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What is the diagnostic criteria for MM?
At least 10% abnormal plasma cells in bone marrow PLUS (1) of the below:
1. M-protein in the serum
2. M-protein in the urine
3. Lytic bone lesions (well-defined radioluencies on radiographs) - redominantly found in the skull and axial skeleton
Splenic sequestration crisis is?
The sudden pooling of blood into the spleen results in rapid development of splenomegaly and hypovolemic shock
- potentially fatal complication of SCD and b-thalassemia) curring more commonly in children because they have intact spleens.
Features of CLL:
1. Asymptomatic - found incidentally on CBC
2. Painless LAD
4. Frequent respiratoy or skin infections 2/2 immune deficiency
5. More advanced disease: fatigue, weight loss, pallor, skin rashes, easy bruising, bone tenderness and abdonminal pain.
Causes of thrombocytopenia:
1. Decreased production 2/2:
a. Bone marrow failure:
aquired aplastic anemia
congenital (Fanconis anemia)
congenital intrauterine rubella
b. Bone marrow invasion:
tumors, leukemia, fibrosis
c. Bone marrow injury: drugs (ethanol, gold, CA chemo agents, chloramphenicol), chemicals (benzene), radiation, infection
2. Increased destruction
a. Immune: infection, DI, ITP,SLE, HIT type 2, HIV-assocaited thrombocytopenia
b. Nonimmune: disseminated intravascular coagulation dIC, Thombotic thromboy=cytopenic purpura (TTP), HIT type I
3. Sequestration from splenomegaly
4. Dilutional - after transfusions or hemorrhage
5. Pregnancy - usually an incidental finding (especially third trimester) but can also occur in setting of pre-eclampsia or eclampsia (remember HELLP syndrome)
Clinical features of Hemophilia A
1. Hemarthrosis (factor VIII) - KNEES most common site
a. progressive joint destruction can occur 2/2 recurrent hemarthrosis
b. maintaining normal factorVIII levelsby prophylactiv administration of factor VIII concentrate can minimize joint dectruction
c. SYNOVECTOMY (arthroscopic) or radiosynovectoy may be needed if recurrent hemarthrosis occurs despite optimatl medical management
2. Intracranial bleeding
a. second most common cause of death (AIDS due to past history of transfusions)
3. Intramusclar hematomas
4. Retroperitoneal hematomas
5. Hematuria or hemospermia
Sickle Cell Anemia
1. Autosomal recessive disorder that results when the normal hemoglobin A chain is replaced by the mutant Hb S. Sickle cell disease is caused by inheritance of two Hb S genes where as sickle cell trait is caused by the inheritance of one HbS gene (heterozygous)
What are the three major subtypes with varying severity of vWD:
1. Type 1 (most common)- decreased levels of vWF
2. Type 2 (less common)-exhibits qualitative abnormalities of vWF
3. Type 3 (least common) - absent vWF (severe dz)
Most common critically ill patients (in ICU) usually are diagnosed with >>> however it can occur in healthy patients as well
-can be acute and fatal or more gradual
Severity of thrombocytopenia and associated risk
1. Platelet count: > 100,000
3. < 20,000
4. < 5,000
1. > 100k: abnormal bleeding (even after trauma or surgery) is usual
2. 20-70K: Increased bleeding hemorrhage during surgery or trauma
3. < 20K: minor spontaneous bleeding: easy bruising, petechiae, epistxis, menorrhagia, bleeding gums
4. < 5K: Major spontaneous bleeding; intracranial bleeding, heavy GI bleeding
Protein C deficiency
-autosomeal dominant inheritence
-inhibitor of factors 5 and 8 thus deficiency leads to unregulated finbrin synthesis
What are the clinical features of ITP:
1. Petechiae and ecchymoses on the skin
2. Bleeding of the mucous membranes
3. NO splenomegaly
Name one intermediate NHL
Diffuse Large-Cell Lymphoma:
1. B-cell origin
2. Middle-aged and elderly patients
3. Locally invasive; presents as large extranodal mass
4. 80% cure rate with CHOP
What is a MACROCYTIC anemia?
1. MCV > 100
2. Vitamin B12 is involved
a. Cofactor in coversion of homocysteine to methionine
b. cofactor in coversion of methylmalonyl CoA to succinyl CoA
3. Vitamin B12 stores in the liver are plentiful and can be sustained for 3 or more yrs
4. Vitamin B12 is bound to intrinsic factor (produced by gastric parietal cells), so it can be absorbed by the terminal ileum.
What is the therapy for AML?
7 + 3
1. 7 days CYATARABINE
2 DAY1-3 WITH DAUNORUBICIN
****WAIT 7 SEVENS DAYS
3. DAY 14 BMBx
IF ANC < 1000 and or platelets <100K --> 5 + 2 which includes
1. 5 days of CYTARABINE
2. DAY 1-2 with DAUNORUBICIN
****WAIT 7 days
3. DAY 12 BMBx
IF STILL blasts after 2nd BMBx post induction and re induction with 5+2, then performthe HiAM treatment
IF ANC > 1000 or PLT > 100K
1. Start CONSOLIDATION therapy which includes: HiDAC + Dasatinib for 21 days
2. Gets three cycles total
What is the prognosis of a patient with SCA? (sickle cell anemia)
Survival correlates with the frequency of vaso-occlusive crisis - the more frequent crisis are associated with a SHORTER LIFESPAN
If there are more than three crises per year, the median age of death is 35 years. Patients with fewer crises per year may live into their 50s. (<3/years = 50YO lifespan)
IN GENERAL, SICKLE CELL DISEASE REDUCES LIFE BY 25-30 YEARS.
How might Hereditary spherocytosis be diagnosed? Treated?
Diagnosed: RBC osmotic fragility to HYPOtonic saline (because it tests ability of RBCS to swell in a graded series of hypotonic solutions and because of their shape, spherocytes tolerate less swelling before they rupture, thus they are OSMOTICALLY FRAGILE and undergo lysis at a HIGHER oncotic pressure.
-INCREASED retic count with elevated MCHC
-Peripheral blood smear would reveal spherocytes
-Direct coombs test result in negative which is helpful to distinguish from AIHA in which spherocytes are also seen
What is the significance of ordering a SCHILLING TEST?
gives information regarding cause of b12 deficiency
-give an IM dose of unlabeled vitamin b12 to saturte binding sites
-give an oral dose of radioactive b12; measure amount of b12 in urina and plasma to determine how much b12 was absorbed
-repeat the test (oral radioactive b12) with the addition of IF. If malabsorption is the problem then adding IF will not do anything. HOWEVER if pernicious anemia is present, then adding IF will improve the serum vitamin B 12 levels.
What is the first step to perform in an anemic patient:
Assess volume status and hemodynamic stability.
If unstable, transfuse PRBCs before attempting to find the cause of the anemia
How to readily treat CLL with chemotherapy:
No current chemotherapy that can permanently treat CLL the only one we current have "treats the grass" - will continue to grow, then "debulk" by chemo but we never get rid of all the "grass" completely. Then eventally grass grows and needs to be "cut" again.
The type of lymphocyte involved and its level of differentiation determines the course of the disease and its prognosis.
B cell lymphocytes account for __% of all cases; T cell lymphocytes acct for ___% of all causes
=disease starts in the node and then spreads to blood and bone rather than node to node as seen in Hodgkins.
Treatment of essential thrombocytosis
1. Antiplatelet agents (anagrelide and low dose ASA)
2. Hydroxyurea if severe
BMB will show increase MEGAKARYOCYTES
Staging system used for Hodgkins lymphoma?
Ann Arbor staging system
Stage I: confined to 1 node
Stage 2: involvvement of two or more lymph nodes but confied to same side of diaphragm
Stage 3: Both sides of diaphargm inovlvedl
Stage 4: dissemination of disease to to extralymphatic sites
Intravascular hemolysis v. Extravascular hemolysis (hemolytic transfusion rxns)
1. Intravascular - ACUTE HEMOLYTIC REACTIONS
-very serious and life threatening - caused by ABO mismatched blood transfused into patient.
-fever, chills, n/v, pain in the flanks/back, chest pain, dyspnea
-complications include hypovolemic shock (hypotension.tachycardia), DIC, RF with hemoglobinuria
-management involves stopping the transfusion immediately and aggressively replacing the fluid to avoid shock and renal FAILURE.
2. Extravascular hemolysis (also called delayed hemolytic transfusion reactions)
-extravascular hemolysis is less severe and in most cases is self-limited; it may occur withint 3-4 weeks after a transfusion
-caused by minor RBC antigen --> If patient is Kell antigen-negative and has anti-Kell IgG antibodies from a previous exposure to the antigen, reexposure of her memnory B cells to Kell antigen on RBC cells will result in synthesis of IgG anti-Kell antibodies. These AB coat all of the Kell antigen-positive donor RBCs, which will be removed extravascularly by macrophages in the spleen, liver, and bone marrow.
-FEVER, JAUNDICE, ANEMIA
-Managment - none, good prog
What are the clinical features of vWD
Cutaneous and mucosal bleeding - epistaxis, easy bruising, excessive bleeding from scratches and guts with gingival bleeding.
Menorrhagia that affects more than 50% of women with vWD
GI bleeding possible
What is lymphoma?
cancers of the lymphatic system in which there are two types:
1. Hodgkins Disease
lymphadenopathy is usually the first finding
Why might a prolonged PT in a patient with cirrhosis be a poor prognostic factor?
Because only in SEVERE LIVER DISEASE does the PT become prolonged
What is waldenstrom's macroglobulinemia?
proliferation of plasmacytoid lymphocytes that produce IgM paraprotein which is large and causes hyperviscosity in the blood.
-DIAGNOSIS WHEN IgM > 5G/DL; BENCE JOINES PREOTEINURI IN 10% of cases - but NOT ANY bone lesions so can r/o MM
What is the classification of NHL?
>20 different subtypes of NHL
-the "working classification system" is the most common and classifies accprding to histologic grade: low grade (indolent), intermediate grade, and HIGH grade
Teardrops on the peripheral smear with bone marrow aspirates showing marrow fibrosis that if severe enough causes a dry tap.
Agnogenic myeloid metaplasia with myelofibrosis
What is the clinical feature of Hodgkins disease:
1. Most common symptom is a painless LAD
2. Supraclavicular cervical, axillary, mediastinal lymph nodes
3. Spreads by continuity from one lymph node to adjacent lymph nodes
4. Other presentations may or may not be present, including B symptoms, pruritis and cough
What is the treatment for SCA?
1. Advise the patient to avoid high altitudes (low o2 tension can precipitate crisis)
2. Maintian fluid intake (dehydration can precipitate crisis)
3. Treat infecions PROMPTLY (infection/fever precipitates crisis)
1. Early vaccination for S. pneumo; H. influ; Pneumovax, Neisseria meningitis
2. Prophylactic penicillin for children until 6YO-start at 4 months
3. Folic acid supplements (due to chronic hemolysis)
5. Management of painful crisis
-morphine for pain
-keep patient warm
6. HYDROXYUREA-enhanves HbF levels which interferes witht he sickling processing and results in reduced incidence of painful crisis and accelerates healing of leg ulcers and may reduce recurrence.
7. Blood transfusion - NOT USED UNLESS NECESSARY!! Based on clinical condition and NOT the Hb levels.
-acute chest syndrome
8. BMT-this has been performed successfully to treat SCA but is not routinely performed due to matched donor avilablilty and risk of copmlications. It may be more cost-effective in the long run that conservative therapy.
Signs of aplastic anemia
1. Fatigue and SOB
2. signs and symptos of thombocytopenia (petechieac, easy bruising
3. Inreased incidence of infections due to neutropenia
4 Can transform into acute leukemia
Causes of spherocytosis include:
1. Hereditary spherocytosis
2. G6PD deficiency
3. ABO incompatibility (but not Rh incompatibility)
5. AIHA (autoIMMUNE hemolytic anemia)
What makes HbS differ from HbA?
The substiution of an uncharged (neutral) valine for a negatively charged glutamic acid at the 6th position of the B chain yeilds a newly POLAR molecule that has a changed structure after the initial binding and release of O2.
Clinical features of Vitamin k deficient coagulopathy:
1. First finding is a prologed PT
2. PTT will begin to diminish as other clotting factors decrease
Fresh frozen plasma (FFP) is used for?
1. Contains all of the clotting factors
2. Contains no RBCs/WBC/platelets
3. Given in patients for high PT/PTT, coagulopathy, and deficiency of clotting factors - FFP can be administered if you cannot wait for Vitamin K to take effect, or if pateint has liver failure (in which cause VK will not work)
4. Follow up PT and PTT to assess response
b. Indication for use
a. MOA- a vitamin K antagonist - leads to a decrease in vitamin K -dependent clotting factors 2, 7, 9, 10 and protein C and S. Causes prolongation of PT (and increases INR).
** it takes 4-5 days for the anticoagulant effect to begin therefore start heparin as well if the goal is acute anticoagulation because heparin has an immediate effect. Once warfarin is therapeuic by checling INR, then stop the heparin and continue warfarin for as long as necessary.
b. same as heparin but used for LT anticoagulation
c. administered orally - must give heparin first as soon as pTT is therapeutic, inititate warfarin. Continue heparin for at least 4 days after starting warfarin. Once INR becomes therapeutic, stop heparin. THe level of INR in most causes is therapeutic from 2-3
-affects male patients primarily
-caused by deficiency or defect of factor 8 coag protein
-bleeding tendency is related to factor VIII activity
What are the clinical features associated with thrombocytopenia?
1. Cutaneous bleeding; petechiae (most common in dependent areas), eccymoses at sites of minor trauma
2. Mucosal bleeding: epistaxis, menorrhagia, hemoptysis, bleeding in GI and genitourinary tracts
3. excessive bleeding after procedures or surgery
4. ICH and heavy GI bleeding can be life threatening and occur when platelets are SEVERELY LOW
5. Unlike coagulation disorder (eg hemophilia) heavy bleeding into tissues and joints (hemarthrosis, hematomas) is not seen in thrombocytopenia!!
How can hemolytic anemias be classified?
1. Hemolytic anemia due to external factors to RBC defects (aquired)
-medications, burns, toxins
2. Hemolysis due to intrinsic RBC defects - most cases are inherited
-hemoglobin abnormality (SCA), hemoglobin C disease, thalassemia
-membrane defects: hereditary spherocytosis; paroxysmal ND (PND)
-enzyme defects: G6PD, PK deficiency
3. Hemolytic anemia INTRAVASCULAR -- within circulation
4. Hemolytic anemia EXTRAVASCULAR--within the RES, primarily the spleen but can include the lymph notes, bone marrow
What is the treatment regimen for ACUTE LEUKS
AML v. ALL?
1. Treatment of emergenies
a. Blood cultures and AB if infectious
b. Blood transusions for anemia anad platelet transfusion for bleeding. If needed
2. Aggressive combo chemo in HIGH doses for several weeks to obtain remission (absent leukemic cells in bone marrow). One remission occurs, maintenance therapy is used for months to years to prevent recurrance
3. ALL - more than 75% children with it achieve complete remission. WHen occur (relapse) usually response to treatment with aggressive therapy adding 15 years to life. Up to 50% of all ALL patients are cured
4. AML: more difficult to treat and doesnt response well to chemotherapy Survival rates are considerably lower dspite intenive treatment. Bone marrow transplant gives the best chance of remission
B-Thalassemia v. A-Thalassemia
B-thal: B production is deficient but synthesis of alpha is unaffected. Excess a-chain bind to and DAMAGE the RBC membrane. Severity depends upon quantitiative amt of mutation
A-thal: there is a decrease in alpha chains which are a component of ALL tpyes of hemoglobin. The b-globin chains form tetramers which are abnormal hemoglobins. The severity depends on th number of gene loci that are deleted/mutated - it ranges from an aymptomatic carrier state to prenatal death
Causes of DIC:
1. Infection (gram neg sepsis most common like N. Meningitis)
2. Obstetrial complication
a. placenta and uterus have increased TFactor
b. amniotic fluid emboli
c. retained dead fetus
d. abruptio placenta
3. Major tissue injury - trauma , major surgery, burns, fractures
4. Malignancy - lungs, pancreas, prostate, GI tract, acute promeylocytic leukemia
5. Shock, circulatory collapse
6. Snake venum (rattlesnakes
Leukemoid reaction versus CML leukemoid reaction:
1. Usually no hepatosplenomegaly
2. Increased leukocyte alkaline phosphatase
3. History of a precipitating event (eg infection - CML
-opposite to the above findings
WHy might coag failure occur in liver?
1. Decreased synthesis of clotting factors
2. Chlestasis leads to decreased vitamin K absorption, which leads to vitamin K deficiency
3. hypersplenism (splenomegaly due to portal hypertension causing thrombocytopenia)
Name 5 causes of Normocytic (MCV 80-99) anemia with a normal to LO reticulocyte index:
1. Bone marrow fibrosis
2. Aplastic anemia
4. Anemia of chronic disease
5. Renal failure
Name three types of a-thalassemia related disorders
1. Silent carriers
2. A-thalassemia trait (or minor) - mutation/deletion of two alpha loci that is common to african americans
3. HB H disease - mutation/deletion of three alpha loci
-hemolytic anemia, splenomegaly
-significant microcytic, hypochromic anemia
-hemoglobin electrophoresis shows HbH
-treatment is same as for paitnes with B thal major (continuous transfusions)
or possible splenectomy
4. Mutatoin/deletion of all found alpha loci-this is either fatal at birth (*HYDROPS FETALIS) or shortly after
Which lab studies should be ordered if suspected hemolytic anemia?
Sideroblastic anemia usually manifests as a ______/_______ anemia simulating iron-def anemia. Only different is that iron studies will show high serum iron levels and low TIBC. In patients with an identifiably cause of vitamin b6 deficiency like _____ or _____, the administration of pyridoxine can easily correct the problem.
drugs or alcohol (isonized)
What makes factor 8 unit (clotting factor)
Has two portions:
1. The coagulant portion (factor 8 coagulant protein) and an antigenic portion (factor VIII antigenic protein). The latter is synonymous with vWF
Under decreased O2 conditions, (acidosis, hypoxia, changes in termparture, dehydration and infection) the Hb molecules polymerize, causing the RBCs to sickle. How do sickled cells affect the vessels?
They cause obstruction leading to ischemia of the small vessels
Diagnosis of Hodgkins lymphoma
1. Lymph node biopsy: REED STERNBERG CELLS is required to make a diagnosis
a. Neoplastic, large cell with two or more nuclei "owl eyes"
b. B-cell phenotype
c. reed sternburg cells seen in other neoplasma
2. INflammatory cell infiltrates which distinguishes it from NHL because these cells present are reactive to the RS cells. These include plasma cells, eosinophils, fibroblasts and T and B cells
3. CXR and CT scan of the chest and abdomen to detect lymph node involvment
4. Bone marrow biopsy - to evaluate bone marrow involvement
5. Laboratory findings - leukocytosis, eosinophilia; level of ESR elevation sometimes corresponds with disease activity
In elderly patients with iron deficiency anemia (normocytic with low reticulocyte) - what must be RULED OUT
What is the treatment for DIC
1. management of condition that caused DIC (infection or obstetrictic or trauma or shock or snake venom)
2. supportive: FFP replaces clotting factors; platelet transfusions; cryo replaces clotting factors and fibrinogen; low dose heparin (IV or SC) inhibits clotting and can prevent consumption of clotting factors.
3. admin O@ and IV fluids, maintain BP and renal perfusion
How is PNH diagnosed?
Ham's test: the patients cells are incubated in acidified serum, triggering the alternative complement pathway,, resulting in lysis of PNH cells but not normal cells
Sugar water test: patients serum mixed in sucrose. In PNH, hemolysis ensues
FLOW cytometry: anchored surface protens CD55 and CD59 are much more sensitive and specific for PNH
Chronic Lymphocytic Leukemia
Most common leukemia that occurs after age 50
-most patients are > 60YO
-most common in Western world
-Monoclonal proliferation of lymphocytes that are morphologically mature but functionally defective - they do not act as functional plasma cells and produce NO antibodies
What is essential thrombocytosis?
Platelets > 600,000
-reactive (due to infection/inflammation, bleeding) and other myeloproliferative dsordes MUST BE EXCLUDED
-manifested by THROMBOSIS (CVA) or by bleeding due to defective platelet function
-LOW MORTALITY but high morbidity
What is sickle cell trait?
1 out of 12 people of african decent carry the sickle cell trait; they are heterogenous. This also appears in ITALIANS, GREEKS, SAUDI ARABIANS
-patients with SCTrait are not anemic and have a NORMAL LIFE EXPECTANCY!
How does sickle cell disease affect the organs below:
1. Blood - chronic HA, aplastic crisis
2. high output CF due to anemia
4. gallbladder disease (stones), splenic infarctions, abdominal crisis
5. painful crisis, osteomylitis, ascascular necrosis
6. Infections, acute chest syndrome
7. hematuria, papillary necrosis, renal failure
8. proliferative retinopathy, retinal infarcts
OTHER lab tests indicative of MMyeloms
-elevated total protein in the serum due to paraproteins in blood *hyperglobulinemia
-Peripheral blood smear shows reuloux formation which resembles a stack of poker chips
-hyperglobulinemia causes the RBCs to stick together
-Urine will be elevated with BENCE JONES PROTEINS
What is the diagnosis of ITP? How do you make it? How is it treated?
1. Platelet count < 20K; remainder of the blood count is normal (unless significant bleeding has occurred in which case the HB/Hct is decreated and the reticulocyte count is increased
2. Peripheral smear shows decreased platelets
3. Bone marrow aspiration shows INCREASED MEGAKARYOCYTES
4. There is an increased amount of platelet associated IgG
Treatment: Adrenal corticosteroids (cortisol) +IVIg that saturates the reticuloendothelial system binding sites for platelet bound self immunoglobulin so thre is less platelet uptake and destruction by the spleen + splenectomy + platelet transfusions for life-threatening and serious hemorrhagic episodes.
1. Bone marrow failure leading to pancytopenia (anemia, neutropenia, thrombocytopenia)
a. Causes: IDOPATHIC - marjoity of cases
-viral infections (Human parvovirus, hepatitis C, hepatitis B, Epsetin Barr Virus (EBV), CMV, herpes zoster, HIV
-Chemicals - benzene/insectisides
Standard v. LMWH
1. STD Heparin
-therapeutic dose is usually given IV, intiated with a bolus of 70 to 80 U'kg and followed by continuous IV infusion (15-18 U/kg/hr infusion). Theraputic PTT is usually between 60-90 seconds. But this varies dependng on situation
-prophylactive dose is given subcutaneously-low dose hepatin (5000U SC every 12 hours). PTT monitoringis not necessary for SC dosing
-theraputic dose (give as a weight adjusted dose)
-prophylactic dose (varies dependingon type of produce)
What are the clinical findings in someone with a coagulopathy 2/2 severe LIVER disease?
-abnormal bleeding- GI is the most common primarily due to varices 2/2 portal hypertension but exacerbated by coagulopathy.
-prolonged PT and pTT especially PT
Reticulocyte index is important because:
1. Initial test to evaluate anemia - indicates whether effective erythropoiesis is occuring in the bone marrow. Effective erythropoiesis is dependent on adequate raw materials (iron, vitamin B12, folate) in bone marrow, absense of intrinsic bone marrow disease (eg asplastic anemia), adequate EPO from kidney, and survival of reticulocytes (no premature destruction before leaving the bone marrow)
Clinical features of inherited hypercoag states
1. Venous thromboembolism (DVT, and PE) are teh most comon. Hypercoaguabile stats are not fiagnosed until the patient has had sever episodes.
2. Suspect an inherited hypercoag state if one or more of the following:
a. The patient has a family history of DVT, PE, thrombotic events
b. the patient has recurrent episodes of DVT, PE or thrombotic events
c. frist thrombotic even efore age 40
d. patient experiences thombosis in usual sites (mesentary, inferior VC, renal veins, verebral veins
What are the phases of MYELOID CELL GROWTH
6. Segmented neutrophils
How does leukemia differ from lymphoma?
Leukemia is characterized by neoplastic proliferation of abnormal WBCS in which accumulate and interfere with the production of normal WBCs as well as the production of RBC and plts resulting in both anemia and thrombocytopenia.
1. The type of WBC affected:
a. Granulocytes/monocytes are affected, myelogenous leukemia present
b. Lymphocytes are affected, then lymphocytic leukemia is present
2. Maturity of cells affected and the rapidity of disease progression
a. acute is rapid and affects immature cells and so immature cells proliferate before having matured.
b. chronic leuk progresses slow and affects mature cells
What are the two varients of G6PD deficiency
Mild form is present in 10% of african american men (a-variant)
-in this form, HA are self-limited beacuse they maintly involve only the OLDER RBCs and spares the younger RBCs (the younger RBCs have sufficient G6PD to prevent RBC destruction) and thus the hemolytic episodes are usually trigger by infection or by drugs like (ANTIMALARIALs, SULFUR CONTAINING AB like TMP-SMX)
MORE SEVERE form is present in people of mediterranean descent. In this form, young as well as old RBCs are G6PD deficiencyt and thus severe HA occurs when exposed to FAVA beans
-Rx requires blood transfusions until drug is elimianted from the body
General characteristics of Thalassemia:
1. Inherited microcytic disorder of the RBC
2. Mutated production of alpha OR beta-globin chain
3. Classified according to chain deficiency (B thal lacks B, a-thal lacks A)
What are the clinical features of G6PD deficiency?
accumulation of unneurtalized H2O2 which denatures Hb precipitating Heinz body formation within RBCs
-HEINZ bodies attach to RBC membranes, reducing their flexibility and making them prone to sequestration by the spleen
-OFTEN DRUG induced and reports with DARK URINE and JAUNDICE on physical exam!
What is the formula for converting Hb into Hct?
Hb x 3 = Hct (IU PRBCS increased Hb level by 1 point and Hct by 3)
What is the treatment for NHL:
3. High grade
1. Indolent forms of NHL are not curable but have a 5 year survival rate of 75% thus OBSERVE, chemotherapy and radiation therapy are good options
2. Intermediate and high grade MAY be curable with aggressive treatmanets but if complete remission is not achieved, survival is less than 2 years. Aggressive treatments include: CHOP and radiation therapy
3. Very high dose chemotherapy with bone marrow transplantation is LAST resort
When might it be appropriate to be put on LT therapy of warfarin?
If two or more thromboembolic events have occured
What is polycythemia vera?
Myeloproliferative disorder in which malignant clonal proliferation of hematopoeitc stem cells leads to an excess erythrocyte production
-inc RBC mass occurs independentally of EPO
-median survival with treatment is ~ 9-14 years
What are myelodysplastic syndromes?
class of aquired clonal blood disorders that are characterized by ineffective hematopoiesis with apoptosis of myeloid precursors. This results in pancytopenia despite a normal or hypercellular bone marrow
-occurs more commonly in elderly patients are slightly more commen in men than in women
1. Platelet count
2. Bleeding time
1. NL or dec
Treatment for ITP
IvIg to force out binding sites in spleen (competitive)
What are the epidemiological associations with NHL
Burkitts lymphoma in regions of africa
Patients with HIV and HIV associated lymphomas
Adult T cell lymphoma in japan and the carribean
Two types of ACUTE LEUKEMIAS
1. Acute myelogenous leukemia (AML)
-neoplasm of myelogenous progenitor cells
-AML occurs mostly in adults (80% of adult acute leuks)
-risk factors include exposure to radiation, myeloproliferative syndrome, Down's syndrome, and chemotherapy (alkylating agents)
2. Acute lymphocytic leukemia (ALL)
-ALL is a neoplasm of early lymphocytic precursors with histology revealing predomiance of lymphosblasts; MOST COMMON IN CHILDREN UNDER 15 YO IN THE US
-most responsive to therapy
-poor prognostics: age <2YO or >9YO; WBC 10^5/mm^3 and/or CNS involvement
-if bcell phenotpye, LDH increase, or rapid leukemic cell proliferation - increased risk for CNS involvement.
Adverse effects of heparin?
heparin-induced thrombocytopenia *HIT-lower incidence with LMWHs
possile osteoporosis - lower incidence with LMWH
-rebound hypercoag after removal due to depression of AT3
Thrombotic thrombocytopenic purpura: ((TTP))
-disorder of platelet consumption - unknown cause
-hyaline microthombi occluse small vessels and any organ may be involved and cause mechanical damage to RBCs (schistocytes on peripheral smear)
-life threatening emergency that is responsive to therapy - if untreated - death occurs in months.
2-anemia (hemolytic) microangiopathic
4-acute renal failure (mild)
5-neurological changes *AMS
In which platelet disorder are platelets abnormally large on peripheral smears?
Bernard souliers syndrome- d/o off adhesion to subendothelium due to platelets glycoprotein GPIb-IX; low platelets but large
When is heparin indicated for use?
Venous thromboembolism: DVT, PE
Acute coronary syndromes: USA, MI
Low dose standard heparin or LMWH for DVT prophylaxis
Atrial fibrillation in acute setting
After vascular bypass grafting (CABG)
B-thalassemia MINOR diagnosis? Treament?
Dx: Hemoglobin electrophoresis
Rx: Not necessary as patients are not transfusion-depending like BthalMAJOR)
What is autoimmune hemolytic anemia? (AIHA)
Production of autoantibodies to RBC resulting in destruction of RBCs - this type of AB produced is either IgG or IgM and determines the prognosis, site of RBC destruction and response to treatment.
How might hemophilia A be diagnosed?
1. Prolonged PTT
2. Low factor VIII coagulant level and normal levels of vWF
3. Detection of factor VIII inhibitor
a. If normal plasma is mixed with plasma from a hemophilliac patient, PTT will becme normal.
a. IF the PTT fails to normalize, this is diagnostic of the presnese of a factor VIII inhibitor
What is Bernard-Soulier Syndrome?
Autosomal recessive disease
-disorder of the platelets adhesion (to subendothelium)due to deficiency of platelet glycoprotein GPIb-IX
-on peripheral blood smear, platelets are abnormally large
-platelet transfusions are contraindicated
What is the MOA of Heparin?
1. Potentiates the action of antithrombin to inhibit clotting factors IIa and Xa
2. Prolongs the PTT
3. Half-life of standard heparin is 1 hour. It is longer for low moleculr weight heparins (LMWH) - longer than 2 hours and up to 24 hours depending on the product
How is NHL diagnosed?
Lymph node biopsy for definitive diagnosis - any lymph node > 1cm for a period > 4 weeks that cannot be attributed to infection should be biopsied
-CT scan (chest abdomen and pelvis) to dettermin the extent of disease spread and patients response to treatment
-serum LDH and B2 microglobulin are indirect indcators of tumor burden
-if ALKphos is elevated, bone or liver involvement is liekly
-if LFTs or bilirubin is elevated, liver invovlvement is likely
-Serum electrolytes, RFT
-Bone marrow biopsy
If patient is neutropenic WITH a fever, what is the goal for PLT count? What is the goal for Hb?
Plt goal is >20
Hb > 8
What is the most common type of thalassemia?
B-thalassemia minor (b-thal) is more common than alpha minor but both are mistaken with thalassemia.
What are the clinical features of DIC?
Bleeding tendency (more common in acute cases)
-bleeding from GI tract, urinary tract, gingival or oral mucosa
-oozing from sites of procedures
-occurs most often in chronic cases. ENd organ infarction may develop, all tissues at risk esp CNS and KIDNEY
Low molecule weight heparin (LMWH)
LMWH mostly inhibit factor Xa (equivalent inhibiton of factor Xa as STD heparin)
=less inhibition of factor IIa (thrombin) and platelet aggregation
=they cannot be monitored by PT or PTT because they do not affect either
Fevers, night sweats, anorexia, weight loss, recurrent infections, easy bruising/bleeding, symptoms of anemia, splenomegaly, hepatomegaly, lymphadenopathy
How is iron deficiency anemia treated?
1. Oral iron supplementation (watch for constipation, nausea, dyspepsia)
2. Parenteral iron replacement
a. Iron dextran (IV or IM)
b. Useful in patients with poor absorption or require > O2 than iron oral therapy can provide
3. Blood transfusion is unstable and Hb concentration is < 7
What is the diagnosis of vWD?
-clinical findings and lab information
-prolonged bleed time but normal platelet count (PTT may be prolonged)
-decreased plasma vWF, decreased factor VIII activity
-reduced ristocetin-induced platelet aggregation
While most HIV patients are prohibited from LIVE vaccinations, which vaccination should be administered to HIV + patients with CD4 count > than 200
MMR because is fatal if otherwise untreated
What are AUER RODS and when might these be present?
granules and eosinophilis rods inside malignant cells and are seen in AML but not ALL
Describe how hemolytic anemia presents in a SCA patient?
-gallstone disease (very common) - pigmented gallstones
-the anemia itself is well compensated and is rarely transfusion dependent
-high-output heart failure may ovver over time (secondary to anemia)-many adults eventually die of CHF
-aplastic crisis: these are provoked by viral infection such as human parvovirus B19, which reduces the ability of the bone marow to compensate. Rx: blood transfusion - the patient recovers in 7-10 days
What is the treatment of HODGKINS lymphoma?
Chemotherapy + radiation therapy to the involved field.
Stage I, II, IIIA can be treated by radiation along
-some will use chemo adjuvant therapy
Stage IIIB or IV require chemo
***chemo+radiation therapy in combination achieve cure rates of over 70% in hodgkins disease
If anemia develops rapidly, what symptoms develop?
If anemia develops gradually?
Rapidly: then symptoms are much more likely to be present bc little time for compensation
Gradually: compensatory mechanisms are able to maintain oxygen delivery and symptoms may be minimal or ABSENT
What is the treatment for PNH?
Glucocorticoids (prendnisone) are the usual initial therapy, but many patients do not respond thus will administer...
Diagnosis of myelodysplastic syndrome:
BONE MARROW BIOPSY
-dysplastic marrow cells
CBC WITH PERIPHERAL SMEAR
-normal or elevated MCV
-HOWELL JOLLY BODIES with BASOPHILIC STIPPLING and NUCLEATED RBC and HYPOLOBULATED NEUTROPHILIC NUCLEI and LARGE PLATLETS
What is the least aggressive type of leukemia with the highest rate of survivial?
CLL; and most survive longer than those with acute leuks or those with CML. The course is variable but typically follows a prolonged indolent course.
More than 75% of patients with hemophilia A and 50% of patients with hemophilia B are _____-positive. These values should be decreasing with time 2/2 modern screening of donor blood. (>1985)
What is monoclonal gammopathy of undetermined significance (MGUS)? How does this differ from MM?
Common in the elderly (up to 10% in patients > 75 Yrs of age)
-diagnosis: IgG spike < 3.5g; less than 10% plasma cellsin bone marrow; bence jones proteinuria < 1g/24 hours.
-fewer than 20% develops MM in 10-15 years
-no treatment necessary; close observation is suggested
Diagnosis of iron deficiency anemia:
1. Decreased serum ferritin - most reliable test available
2. Increased TOTAL IRON BINDING CAPACITY
3. Elevated transferrin levels
4. Decreased serum IRON
5. Microcytic, hypochromic RBCs on peripheral smear
6. Bone marrow biopsy-GOLD STD
7. Guaiac stool test - if GI bleed is suspected
What are the two forms of ITP?
1. Acute form: seen in children, preceded by a viral infection (in most cases); usually self-limited - 90% resolve spontaneously within 6 months
2. Chronic form: seeen in adults most commonl women between 20-40 YO; spontaneous remissions are rare
What is the prognosis of multiple myeloma with treatment? WIthout treatment? 5 year survival rate?
With treatment = 2-4years
Without treatment = 6 months
5 year survival = 10%
What are the clinical features of MM?
1. Bone pain due to osteolytic lesions in the low back or chest (ribs) and jaw (mandible)
2. Pathological fractures
3. Loss of height 2/2 collapse of vertebrae
Anemia (normocytic normochromic)-present in most patients due to bone marrow infiltration adn renal failure
Renal failure - mainly due to:
1. Myeloma nephrosis = immunoglobulin precipitation in renal tubules leads to tubular casts of Bence Johnees protein and hypercalcemia also plays a role in renal dcompensation
Recurrent infections - 2/2 deprivation of normal Ig; therfore hemoral immunity is affected
-MOST COMMON CAUSE OF DEATH - UP TO 70% OF PATIENTS DIE OF INFECTION (LUNG OR URINARY TRACT IS THE MOST COMMON)
What is the treatment of AIHA?
1. No treatment necessary in either type of AIHA because the hemolysis is MILD. If it is more severe, the erapeutic approach depends upon the typ of autoantibody causing it.
-WARM AIHA: glucocorticoids are the mainstay of therapy.
-splenectomy - use for patienst whose condition does not responds to glucocorticoids
-folic acid supplementation
-COLD AIHA: avoiding cold exposure prevents hemolysis and anemia
-RBC transfusions if absolutely necessary
-various chemotherapeutic agents
-steroids are NOT beneficial
Treatment of aplastic anemia
Bone marrow transplant
Transfusion of PRBCs and platelets, if necessary *use judiciously
Thrombocytopenia can result in clinical features that includes:
ecchymosis, nasal bleeding, mouth ulceration/gum bleeding, GI tract, ICH
Lo reticulocye (<2%) with macrocytic anemia (>100)
1. Check B12 and folate levels
2. Abnormal B12/folate --> diagnostic
3. Normal - then suspect LIVER DISEASE
What is the diagnosis of Hb and Hct:
1. Formula to convert Hb to Hct: Hb x 3 = Hct (1 unit of packed RBCs [PRBCs]) increases Hb level by 1 point and Hct by 3 points
2. If patient has good cardiac function and intravascular volume is adequate, low Hb and Hct levels are tolderated even an Hb of 7 or 8 provides sufficient O2 carryng capacity for most patients however anemia is not tolerated as well in patients with impaired cardiac function
How is SCA diagnosed?
1. Anemia is the most common finding.
2. Peripheral smear - sickle shaped RBCs
3. Hemoglobin electrophoresis is REQUIRED for diangosis in most casis, diagnosis is made from newborn screening tests!
Diagnosis of CLL
CLL: a cancer of B-lymphocytes
-to diagnose CLL - there is NOT ONE PARTICULAR GENETIC ABNORMALITY THAT IS PATHOPNEUMONIC (unlike that of CML in which has the t(9; 22) genetic abnormality)
-We do not have a molecular-marker, instead look at pattern (Look @ CD19, 20, 23
-Find B cells that have abnormal expression of CD5 (t cell marker) in normal cells - shouldn't have both CD20 and cd5 positive B cells because abnormal to express a T CELL marker CD5
-Thus can make diagnosis by FLOW cytometry of the peripheral blood.
-Look for population of cells that has the t cell markers 50% of the time gets diagnosed incidentally asymptomatic usually but if they do -- will have the origniation of b cells in bone marrow then go to lymph nodes and cause to swell
-if too many CLL cells in marrow, can cause some pancytopenias due to proliferation
What is the difference between HIT type I versus type II?
HIT type I = heparin directly causes platelet aggregation seen < 48 hours after initiating heparin; no treatment needed (NONIMMUNE)
HIT type II = heparin induces antibody-mediated injury to paltelet; seen 3-12 days after intiiating heparin; discontinue HEPARIN IMMEDIATELY!
What are the clinical features of irondeficiency anemia:
dyspnea on exertion
hypotension, if acute, tachycardia
Disorders of blood coagulation:
1. von Willebrands Disease (vWD)
-autosomal dominant d/o with deficiency or defec of factor VIII-related antigen (vWF)
-vWF enhances platelet adhesion and aggregation (first two steps in platlet flot formation)
-carrier of factor VIII (8) in blood
****MOST COMMON INHERITED BLEEDING D/O (1-3% OF US)
PT v. PTT v. Thrombin time v. Bleeding time
PT: reflects extrinsic pathway (prolonged by warfarin)
PTT: reflects the intrinsic pathway (prolonged by heparin - factor X)
thrombin time: measures fibrinoen concentratoin
bleeding time: reflects platelet function
What is the treatment of/for CLL
Chemotherapy has little effect on survival but good for symptoms.
1. FLUDARABINE AND CHLORAMBUCIL have been shown to be of some benefit.
Major clinical features associated with SCA?
1. Severe lifelong hemolytic anemia
2. Findings secondary to vasal occlusion
a. Painful crisis
b. Hand-foot syndrome (dactylitis)
c. Acute chest syndrome
d. repeated episodes of splenic infarctions
e. avascular necrosis of joints
h. Opthalmologic complications
i. Renal papillary necrosis with hematuria *painless
j. Chronic leg ulcers
k. abdominal crisis
3. infectious complications
a. functional asplenia results in increased susceptibility to infections of encap
bacteria that includes (S. pneumo, H. Influ)
b. predisposition to that of salmonella osteomyelitis (also due to splenic malfunction)
4. Delayed growth and sexual maturation, especially in boys.
Hyperviscosity, headache, dizziness, weakness, pruritis, visual impairment, dyspnea
with thrombotic phenomena (DVT, PE, VIA, MI, portal vein thrombosis) or BLEEDING -GI or GU bleeding with HTN
High-grade NHL (name 2)
1. Lymphoblastic lymphoma: T-cell lymphoma; more common to children, can progress to T-ALL in which 50% have B symptoms; aggressive with rapid dissemination
2. Burkitts (small non-cleaved cell) lymphome: T cell lymphoma common to children. Two types (one in AA involving face and jaw and the other that is american with hepatomegaly and abdominal masses with LAD). AA linked with EBV infection and assicated with t(8; 14)
MGUS v. MM
1. IgG spike < 3.5g
2. Less than 10% plasma cellsin bone marrow
3. Bence jones proteinuria < 1g/24 hours.
-fewer than 20% develops MM in 10-15 years
-no treatment necessary; close observation is suggested
1. >10% abnormal plasma cells in marrow
2. Mprotein in serum, urine
3. lytic bone lesions
Causes of myelodysplastic syndromes:
3. immunosuppressive agents
HIV-associated lymphomas include:
Not a discrete entity; usually Burkitts high grade, or diffuse large t cell intermediate grade
What is autologous stem cell transplant and when is this used?
Autologous HSCT requires the extraction (apheresis) of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow function to grow new blood cells). The patient's own stored stem cells are then returned to his/her body, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection (graft-versus-host disease) is very rare due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma. However, for others such as Acute Myeloid Leukemia, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, and therefore the allogeneic treatment may be preferred for those conditions. Researchers have conducted small studies using non-myeloablative hematopoietic stem cell transplantation as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising; however, as of 2009 it was premature to speculate whether these experiments will lead to effective treatments for diabetes.
What is the diagnosis for patiens iwth suspected inherited hypercoag states
Functional assays are available for at3 AB, protein C, S, factor V leigen, prothrobin gene adn hyperhomocystinemia
What is WARM versus COLD AIHA?
Warm AIHA = most common
-autoantibody is IgG which bindsoptimally to RBC membranes at 37 degrees
-results in extravascular hemolysis - primary site of RBC sequestions is the spleen. Splenomegaly is a common feature.
-causes: idiopathic; secondary to lymphomas, leukemias (CLL) and other leukemias, malignancies, CVD (especially SLE!!), and drugs such as alpha-methyldopa
COLD AIHA = autoantibody is IgM which optimally binds to RBC membrane at cold temperatures (usually 0-5 degrees)
-produces compleent activation and intravascular hemolysis and the primary site of RBC sequestration is that of the LIVER
-causes: idiopathic (elderly) or due to infection (such as mycoplasma pneumonia infection or infectious mononucleosis).
WHat are the options for DVT prophylaxis?
2. Low dose unfractionated heparin (UFH)
3. Pneumatic compression boots
What type of anemia can lead to CHF (with symptoms of hemochromatosis)? Why?
B-thalassemia major because requires continuous transfusions leading to IRON overload that can develop. If untreated, these patients are at risk for severe cardiac issues and are often treated with desferrioxamine A CHELATNG AGENT THAT ELIMINATES EXCESS IRON)
What is the treatment for patients diagnosed with B12 deficiency?
Parenteral therapy if preferred - cyanocobalamin (vitamin B12) IM once per month
Lab tests to diagnose hemolytic anemia:
Elevated reticulocyte count
Fibrosis of bone marrow resulting in pancytopenia and extramedullary hematopoiesis. Not surprisingly, massive splenomegaly is usually present. Other manifestations are secondary to pancytopenia (fatigue, bleeding, infection)
Agnogenic Meyloid Metaplasia with Myelofibrosis
Hodgkin type A or Hodgkin type B
Type A: No symptoms
Type B: Fever, weight loss, night sweats, (constitutional symptoms worsens the prognosis)
When are PRBCs transfused? (no plt or clotting factors)
1. MIX with NS to infuse faster (not with lactated ringers solution because calcium causes coagulation with the IV line.
2. Each UNIT of PRBC raises Hct by 3-4 points
3. Admin 2U - each U may be given to adult over 90-120 minutes
4. Check CBC after the transfusion is completed
How is macrocytic anemia diagnosed?
Peripheral blood smear
-megaloblastic anemia (macrocytic RBCs - MCV > 100)
Serum bitamin B12 is low (<100 pg/mL)
Serum methylmalonic acid and homocysteine levels - elevated in vitamin B12 deficiency and are useful if B12 is borderline. Will notice if treatment with folate.
What does the RDW measure?
the variation in RBC size. RDW is usually abnormal in irondef anemia but is generally normal in all of the other microcytic anemias.
What is the pathology of hereditary spherocytosis?
Autosomal dominant inheritance of a defect in gene coding for the SPECTRIN and other RBC proteins. Spectrin content is deeased but is not totally absent. There is a loss of RBC membrane surface area without a reduction in RBC volume. Necessitating a spherical shape. The spherical RBCs become trapped and destroyed in the spleen by macrophages hence the term extravascular hemolysis
Inherited hyperCOAG states?
1. Antithrombin III deficiency
2. Antiphospholipid antibody syndrome
3. Protein C deficiency
4. Protein S deficiency
5. Factor V leiden
6. Prothrombin gene mutation
Features of NHL?
-superior vena cava obstruction, respiratory involvement, bone pain
Treatment for Angogenic myeloid metaplasia with myelofibrosis?
Supportive with transfusions, eruthropoitin and splenectomy for palliative relief of painful splenomegaly
BMT is sometimes appropriate
Normal bleeding time:
1. 11-15 seconds = PT (2, 7, 9, 10, C, S)
2. 25-40 secondar = PTT (factor X = intrinsic)
3. 2-7 minutes = bleeding time (PLATELETS)
What is CML
-neoplastic clonal proliferation of myeloid stem cells (plt, erythro, granulo)
-CML is indolent *chronic course for many years before it transforms into ACUTE leuks.
-end point of diesase is usually acute phase or a "BLAST CRISIS"
-associated with t(9;22) phildelphia chromosome that is present in >>>>90% of patients
What is the treatment for the anemia type in the below picture (what is the most important step in treatment)?
1. avoid drugs that precipitate hemolysis
2. maintain hydration
3. perform RBC transfusion when necessary
Treatment of vWD
1. DDVAP (demopressin) induces endothelial cels to secrete vWF.
-rx of choice for type 1 vWD
-some with type 2 may respond but not if type 3
2. Factor VIII concentrates with high molecular weight vWF
-give to all patients with vWD of any type after trauma or during surgery
-good for type III and type II not responding to DDVAP
3. Cryoprecipitate is NOT recommened as treatment because it carries a risk of VIRAL transmission
4. do not use ASA/NSAIDS - exacerbates bleeding tendency
Treatment of vitamin K deficiency
1. Vit K replenishment (oral or SQ) - may take a few days for PT to return to normal
2. If bleeding is severe and emergency treatment is necessary, FFPshould be transfused
In patients with prior heart disease, what hemoglobin level should be maintained?
Hgb > 10
admin 1U pRBC if abnormally low
WHAT IS PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
-affects hematopoietic stem cells and cells of all blood lineages
-caused by a deficiency of anchor proteins that link complement-inactivating proteins to blood cell membranes. The deficiency of this achoring mechansim results in an unusal susceptibility to completment -mediated lysis of RBCs, WBCs and platelets.
Microcytic Anemia: cause due to IRON DEFICIENCY
Causes = chronic blood loss
1. Most common cause of iron deficiency anemia in adults
2. Menstrual blood loss is the msot common source (in the absense of menstrual bleeding, GI blood loss is most likely
Causes = dietary deficiency/increased iron requirements-primarily seen in these three age groups:
1. Infants and toddlers- occurs is diet is predominantly human milk (low in iron). Children in this age group also have increased requirements for iron because of accelerated growth. Most common between 6mo-3YRS
2. Adolescents-rapid growth increases iron req. Adolescent women are at high risk of irondeficiency microcytic anemia
3. Pregnant women - increases iron req
Adverse effects of warfarin
2. Skin necrosis is a rare but serious complication caused by rapid decrease in protein C *a vitamin K dependent inhibitor of factor 5 and 8a
3. Teratogenic during pregnancy
4. should not be given to alcoholics or to any patient prone to frequent falls because intracranial bleed in a patient on warfarin can be catastrophic
How might VB12 and folate deficiency differ in clinical symptoms:
1. SImilar to those in vitamin b12 deficiency without the neurological symptoms
What is TUMOR LYSIS SYNDROME
Potential complication of chemotherapy seen in acute leukemia and high grade NHL (burkitts)
-Rapid cell death leads to the release of intracellular contents that causes hyperkalemia, hyperphosphaemia and hyperuricemia
What is the treatment of thrombocytopenia?
Treat the underlying cause
-platelet transfusion- use depending on he cause and severity of thrombocytopenia
-discontinue NSAIDS and other antiplatets agents and anticoags
WARM AIHA is often seen in which type of leuks?
Patients with CML, the course of CML is mroe aggressive than CLL
How is hemolytic anemia diagnosed?
1. Hb/Hct level depends upon degree of hemolysis and reticulocytosis
2. Elevated reticulocyte count due to increased RBC production
3. Peripheral smear (schistocytes or helmet cells)
4. Haptoglobin levels - low in HA - haptoglobin binds to hemoglobin so its absense means that hemoglobin was destroyed.
5. Direct coombs test (detects AB or completment on RBC membrane) - positive in autoimmune HA
6. Osmotic fragility
Treatment of myelodysplasic syndromes:
-RBC and platlet transfusions
-EPO may help to reduce the number of blood transfusions necesary
-Granulocyte colony-stimulating factor can be an effective adjunctive tretament for neuropenic patients
-vitamin supplementatin particularly with B6, 12, folate, is important gievn the large turnover of marrow cells.
Pharmocologic therapy has variable results:
1. Immunosuppressive therapy
3. Androgenic steroids
BMT is the only cure
What is the purpose of the MCH and MCHC?
Little value clinically. THey are neither sensitive nor specific for any diagnosis however the MCV is very valuable in diagnosing the cause of anemia.
How is B-thalassemia MAJOR diagnosed? Treated?
Diagnosis: Hemoglobin electrophoresis (HbF elevated); peripheral blood smear (microcytic hypochromic anemia
Treatment: Frequent PRBC transfusions to sustain life
What is multiple myeloma?
Neoplastic proliferation of a single plasma cell line that produces monocloncal immunoglobulins. This leads to enormous copies of one specific immunoglobulin (IgG or IgA) in the over 50YO individual.
-most common in african americans
-as the disease progesses, bone marrow elements are replaced by the malignant plasma cells therefore anemia, leucopenia and thrombocytopenia may be present in advanced disease.
Diagnostic criteria for polycythemia vera
Must have all three major criteria or any two major and 2 minor to be diagnosed:
1. Elevated RBC (men > 36; females >32)
2. Aterial O2 sat > 92%
1. Thrombocytosis (>400 platelet count
2. Leukocytosis > 12 x 10^9/L
3. Leukocyte alk phosphatase (>100) without fever or infection
4. Serum vitamin b12>900
What is the treatment of Hemolytic anemia:
1. Treat underlying cause
2. Transfusion of PRBCs if severe anemia is present or patient is hemodynamically 3. compromised
Folate supplementation (folate is depleted in hemolysis)
What are the clinical features of anemia
1. Nonspecific complaints (headache, fatigue, poor concentration, diarrhea, causea, vague abdominal discomfort
2. pallor - best noted at conjunctive
3. Hypotension and tachycardia
4. Signs of the underlying cause - jaundice if HA, blood in stool if GI bleeding.
Vitamin K deficiency:
Vitamin K is required for: 2, 7, 9, 10, protein C/S
-process is post translational modification
-source of vitamin K is by diet leafy greens and bacteria in the gut
-CAUSES of VITA K deficiency:
a. broad spec AB that suppressed gut flora in patients who are NPO
b. Patients on TPN (unless vitamin K delivered)
c. Malabsorption of fat solubl vitamins in the (SBO, inflammatory disease, celiac, pancreatits, jaundice)
d. Warfarin - a vitamin K antagonist (causes production of INACTIVE clotting factors)
Reversal of heparin versus reversal of warfarin:
Warfarin - d/c and administer vitamin K
-halflife of warfarin is much longer than that of heparin and it takes 5 days to correct the effects of warfarin on stopping the medication. Vitamin K infusion corrects the abnormal PT within 4-10 hours if thepatient has normal liver function
-giving vitamin K makes it difficult to return the patient to therapeutic INR levels if anticoagulation is to be continued
A reticulocyte index > 2% implies
excessive RBC destruction or loss. The bone marrow is responding to increased RBC requirement
What are the general characteristics of anemia?
1. Reduction in EITHER hematocrit or hemoglobin
2. When red cell mass (as measured by Hb or less precisely by Hct) decreases, several compensatory mechanisms maintain oxygen delivery to the tissues.
a. increased CO (heart rate and stroke volume)
b. Increased extraction ratio
c. Rightward shift of the oxyhemoglobin curve (increased 2,3DPG)
d. Expansion of plasma volume
3. Blood transfusions are not recommended unless <7 g/dL Hgb or the patient requires increased O2 carrying capacity (patients with coronary artery disease or some other cardiopulmonary disease)
1. Platelet count
2. Bleeding time
Diagnosis for apastic anemia
Perform a bone marrow biopsy for definitive diagnosis-this reveals hypocellular marrow and in the absense of progenitors of all three hematopoietic cell lines.
What is DIC?
characterized by the abnormal activation of the coag sequence, leading to formation of microthrombi throughout the microcirculation. This causes consumption of platelets, fibrin, and coagulation factors Fibrinolytic mechanisms are activated leading to hemorrhage. Therefore, bleeding and thrombosis occur simultaneously
Secondary causes of hypercoaguable states or risk factors
2. Antiphospholipid antibody syndrome
4. Immobilization, causign stasis of blood
5. Myelo[rpliferative disorders
7. Postoperative state (especially after ortho procedures)
9. Nephrotic syndrome
10. HIT or DIC
12. CHF - stsis of blood
HOW DOES VWF DIFFER FROM FACTOR VIII COAG PROTEIN?
vWF (Factor 8-related antigenic protein)
1. produced in endothelial cells and megakaryocytes
2. platelet adhesion - mediates the adhesion of platelets to the injured vessel walls (ie reacts with platelet GPIbIX and subendothelium)
3. Binds the factor 8 coagulant protein and protects it from degradation
4. inheritance pattern of vWF - AD
5. vWD has low vWF
6. Hemophilia is NORMAL
Factor 8 coag protein
1. produced in the liver
2. functions as fibrin clot formation
3. Xlinked recessive
4. vWF is reduced but not low
6. VERY LOW hemophilia
Treatment of CML:
1. Chemo to control symptoms before acute phase blast crisis develops
2. Blast crisis is usually terminal with high dose chemo may be used to return dz to chornic
3. Alkylating agent or antimetaolic can be used
3. Bone marrow or stemp cell transplate becase most cases will eventaully become an acute phase.
Low hemoglobin, high calcium, high serum protein, and poor renal function suggest multiple myeloma.
1. Bone marrow replacement by plasma cells
2. PTHrP and degradation
3. High protein content to due immunoglobulins and poor renal function with light chains being passed through the glomerular capsule.
Values of serum ferritin/iron/TIBC/RDW in:
1. Iron def anemia
2. Anemia of chronic disease
1. Low ferritin, low iron, high TIBC and HI RDW
2. Normal to HI, lo serum iron, low TIBC and normal RDW
3. Normal to HI serum ferritin, normal/high iron, normal TIBC, RDW normal to HI
Which aggressive NHL with rapid dissemination responds well to combination chemotherapy?
How is polycythemia vera treated?
1. Phlebotomy to lower hematocrit
2. Myelosuppression with hydroxyurea or recombinant interferon alpha (rIFNa)
1. Platelet count
2. Bleeding time
What are the stages of CLL?
Stage 0 CLL - just lymphocytosis :
-because small, no proteins on outside to make sticky - do not "smudge" in blood so no symptoms thus is NOT a reason to start treatment - DO NOT TREAT BASED ON WBC count
Stage I CLL - lymphocytosis with LAD:
-Not all LAD are symptomatic from it if symptoms LAD then this is a reason to pull the trigger to start chemo.
Stage II CLL - lymphocytosis with SPLENOMEGALY
-not all splenomegaly causes symptoms but if regurgitation, n/v, early satiety 2/2 enlargement - then reason to put on chemo
Stage III CLL - anemia Hb < 11; with lymphocytosis
-ONLY USE CHEMO if anemia is 2/2 increased proliferation of lymphocytes.
-IF 2/2 iron def/b12/folate/HA then the chemotherapy will NOT treat the CLL
Do a bone marrow and look at to see if low levels of precursor cells with lymphocytosis anemia specifically due to the CLL not to iron impaired normal hematopoeisis - reason to treat!
Stage IV CLL - thrombocytopenic specificially 2/2 CLL always check iron, b12, etc.; Always check ITP, AIHA; AIHA - LDH bili hapto and direct and UA - ITP
For the diagnosis of CML, what is required for diagnosis?
For CML - MUST HAVE T(9; 22) to make diagnosis or else NOT CML
1. THREE PHASES OF MYELOID BLAST CRISIS include:
(a) CHRONIC <5%
(b) ACCELERATED 6-19% BLASTS
(c) BLAST CRISIS >20% BLASTS
-WHEN SOMEONE HAS CHRONIC PHASE CML, THEN THE STEM CELL WITH ITS (9;22) TRANSLOCATION IS QUIET. WHAT IS OUT OF CONTROL IS THE MYELOID STEM CELL FOR CHRONIC
-BUT IF THE HEMATOPOEITIC STEM CELL GETS A SIGNAL, CAN GET ACTIVATED AND START DOWN THE LYMPOID too which results in the diagnosis of CML with lymphoid crisis (so will have a 210kDA breakpoint with t(9;22) and > 90% lymphoblasts)
*****normally, shouldnt see immature cells in the blood. If you see blasts then bc too many to fit and growing at such rapid rate.
THe peripheral blood of CML in a patient looks like that of the normal bone marrow biopsy in a patient
-genetic abnormality (9; 22) - philadelphia chromosome
even though change by genetics, will STILL get maturation
What are the clinical features of Acute leuks?
1. Anemia, increased risk of infection 2/2 neurtropenia
2. Pneumonia, UTI, cellulitis pharyngitis, esophagitis
high mortality and morbiditiy
3. Abnormal mucosal or cutaneous bleeding (2.2 thrombocytopenia)
4. HSM, LAD
5. Bone and joint pain
6. CNS involvment - diffuse or focla neurologic dysfunction (meningitis)
7. Testicular involvement (ALL)
8. Anterior mediastinal mass (Tcell ALL)
9. Skin nodules (AML)
Dark urine + jaundice + heinz bodies on blood smear = by ingestion of which drugs?
G6PD deficiency 2/2 SULFONAMIDES, NITROFURANTOIN, PRIMAQUINE, DIMER-CAPROL, FAVA BEANS, INFECTION
Cryoprecipitate is transfused in a case of?
For patients with hemophilia A, decreased fibrinogen (DIC), and vWD. Contains factor VIII and fibrinogen
What is CHOP therapy and when is it used?
CHOP - intermediate/high grade lymphoma (NHL)
H- hydroxydaunomycin (doxorubicin - can cause cardiomegaly)
O- oncovin (vincristine)
Which clotting factor has the shrotest halflife and thus makes the first laboratory finding be a prolonged +++
Factor VII has the shortest half life of (3-5) hours so the PT will be prolonged first to >11-15 seconds
How is DIC diagnosed?
Elevated PT, PTT, bleeding time and TT, Fibrin split products (activation of fibrinolytic system), D-dimer
Decreased fibrinogen, platelet count, peripheral smear reveals schistocytes (damage from RBCs as they go through the microcirculation with microthrombi)
Why might a burning sensation be noted in patients with essential thrombocytosis
erythromelagia is a burnging pain and erythemia of the extremeitie due to microvascular occlusions.
In TTP, there is no consumption of ____ ______, so the PT and PTT will be NORMAL. What are the signs of TTP? OR what are the signs of HUS?
CLotting factors are fine - liver still producing them
1. TTP = HUS + fever + AMS
2. HUS = Thrombocytopenia + acute renal failure + hemolytic anemia (microangio)
Distribution of Hodgkins lymphoma?
Bimodal - 15-30YO and >50YO
-lymph node histology divides disease into four subtypes
a. Lymphocyte predominance 10-20% - few reed sternburg cells and Bcells
b. Nodular sclerosis (40-60%) occurs more frequently in women with bands of collagen envelope pools of RS cells
c. Mixed cellularity (20-40%) large number of RS cells in pleomorphic background.
d. lymphocyte depletion (1-10%)-lacking in mix of reactive cells, associated with the worst progonsis
Normocytic anemias: Anemia of chronic disease
1. Occurs in the setting of chronic infection (TB, HIV, lung abscess), cancer (lung, breast, Hodgkins disease), inflammation (RA, SLE) or trauma.
2. The release of inflammatory cytokines which has a suppressive effect on eryothropoiesis.
Lab findings: low serum iron and low TIBC, and low serum transferrin levels occur. Serum ferritin levels are increased
How to diagnose the cause of anemia:
1. Look at the _______ index if >2 or <2%
2. If elevated (>2%) then the anemia is due to either _____ or ______.
3. If normal or (<2%) then look at the ______
4. Three types of MCV include:
5. If MCV < 80, what is next to be checked? Leads to result into:
2. Blood loss or Hemolytic anemia
4. Microcytic (<80); Normocytic (80-99); Macrocytic (>100)
5. Check iron studies: look at both IRON and TIBC
-If <80 MCV, and iron studies show decreased iron and decreased TIBC then diagnosis is probably ANEMIA OF CHRONIC DISEASE
-If <80 MCV, and iron studies show decreased iron and increased TIBC, then diagnosis is IRON DEFICIENCY ANEMIA
-If <80 MCV and studies show normal Fe2+ and TIBC that is low or decreasing: lead poisoning or thalassemia
What is pseudoanemia:
Decrease in hemoglobin and hematocrit secondary to dilution (secondary to acute volume infusion or overload)
AT3 deficiency doesnt repond to Rx of heparin, why?
Because heparin requires the presense of AT3 to anticoagulate. If AT3 is defieienct (what directly inhibits thrombin) then increased thrombi can form
Folate deficiency and the general characteristics as a macrocytic anemia
1. Folic acid stores limited
2. Inadequate intake of folate over a 3-month period can lead to deficiency
3. Green vegetables are the main source of folate. Overcooking vegetables can remove folate
What are the risk factors for NHL?
History of EBV or HTLV-1
History of H. pylori gastritis
autoimmune disease (Hashimotos, SLE, SS, MALT)
General evaluation in patients with LEUKEMIA (acute or chronic)
1. Evidence of infection
2. Evidence of bleeding or easy bruising
5. Signs of anemia
6. Fatigue and weight loss.
what causes macrocytic anemia?
pernicious anemia (lack of IF)
crohns disease, ileal resection (terminal ileum)
organisms: diphyllobothrium latum infestation (tapeworm), blind-loop syndrome bacterial overgrowth*****
Why is a TTE ordered for a leukemic pt on admission?
Because can result in abnormal ejection fraction 2/2 AML
Contraindications to heparin:
1. Previous HIT
2. Active bleeding, GI bleeeding, intracranial bleeding
3. Hemophilia, thrmbocytopenia
3. Severe HTN
4. Recent surgery on eyes, spine and brain
Causes of folate deficiency leading to macrocytic anemia?
1. Inadequate dietary intake "tea and toast"
3. LT use of oral AB
4. Increased demand
7. Use of folate antagonists such as MTX
8. Anticovulsant medicatiosn (phenytoin)
Relavant findings in patient history regarding hemolytic anemia:
2. ethnic background
3. family background
What is the treatment for TTP:
1. Plasmaphoresis (large volume)
2. Begin as soon as dianosis is established (delay in treatment if life-threatening)-response is usually good (monitor platelet count) which should increase
3. Corticosteroids and splenectomy - may be of benefit in some cases
4. Platelet transfusions are contraindicated
What is GLANZMANNS THROMBASTHENIA?
Autosomeal recessive d/o (like Bernard Souliers Syndrome)
-disorder of platelet aggregation due to DEFICIENCY in platelet glycoprotein GPIIb-IIIa *on the actual platelet itself that doesnt allow it to bind to R on other cells)
-will prolong the bleeding time because platelets will not adhere or clot
-the platelet count will be normal because no damage to platelet is being done - it is a lack of receptor ON the platelet (in bernard souliers, is lack of receptor on the subendo)
How might heparin/LMWH be reversed?
1. The half life of STD heparin is short (one hour) so it will cease to have an effect within four hours of its cessation.
2. Can give PROTAMINE SULFATE to reverse the effects of heparin if necessary (effectiveness isnot proven)
3. LMWH has a longer half-life than STD heparin, so it takes longer for the effects to fade
-administer FFP if severe bleeding occurs for patients on either warfarin or heparin
What is the treatment for hemophilia A
1. acute hemarthrosis
-analgesics (codeine with or without acetominophen) avoiding all ASA/NSAIDS
-immobilize joint, ice package , non weight bearing movements
2. CLotting factor replacement
-factor 8 concentrate is the mainstay of therapy (both plasma derived and recombinant factor 8 are available)-for acute bleeding episodes and before surgery or dental work.
-cryoprecipitate and FFP are not recommended 2/2 the risk of viral transmission
3. DDVAP - helpful in patients with mild disease. it can increase the levels of factor 8 up to 4x
4. Gene therapy is the next step in future for rx
Coagulopathy of the LIVER disease
1. All clotting factors are produced by the liver (except vWF)
2. Liver disease must be severe for coagulopathy to develop. Therefore if the coagulopathy is due to liver failure the overrall prognosis for the patient is very poor.
*****normally, shouldnt see immature cells in the blood. If you see blasts then bc too many to fit and growing at such rapid rate.
TRUE OR FALSE:
The peripheral blood of CML in a patient looks like that of the normal bone marrow biopsy in a patient
genetic abnormality (9; 22) - philadelphia chromosome
even though change by genetics, will STILL get maturation
Diagnosis of acute leukemias
1. Variable WBC count but there will be a significant number of blast cells (immature) preset in peripheral blood
5. Electrolyte disturbances (hyperuricemia, hyperkalemia, hyperphosphatemia)
*****REQUIRES BONE MARROW BIOPSY FOR DIAGNOSIS! Replacement of marrow by blasts should be the finding
T or F: ALL causes of anemia are initially normocytic because it takes some time for the abnormal sized RBCs to outnumber the normal-sized ones
How might someone with PNH present? (Clinically)
1. chronic intravascular hemolysis - results in chronic paroxysmal hemoglobinuria with elevated LDH
2. Normochromic, normocytic anemia unless iron deficiency anemia is present
4. Thrombosis of venous systems can occur for example if the hepatic veins (BUDD CHIARI) syndrome.
5. May evolve into aplastic anemia, myelodysplasia, myelofibrosis, and acute leukemia
6. abdominal pain, back pain, and MSK pain
Caused by abnormality in RBC iron metabolism
1. Can be hereditary or acquired-
a. Acquired causes include DRUGS (chloramphenicol, INH, alcohol, lead exposure, collagen vascular disease, neoplastic disease (myelodysplastic syndromes)
b. clinical findings: increased serum iron, ferritin, normal TIBC; ringered siderolasts in bone marrow. Traetment remove offending agents (consider pyridoxine.
Why is it imperative that megaloblastic anemia 2/2 folate versus b12 deficiency?
Treatment by folate suplement can improve the anemia of b12 deficiency but not the neurologic impariment. If the b12 deficiency remains untreated, irreversible neurologic disease results
What blood products are capable of being transfused?
1. Packed RBCs (no platelets or clotting factors)
2. Fresh frozen plasma
4. Platelet transfusions
5. Whole blood
clinical features of myelodysplastic syndromes?
Asymptomatic in early stages
-pancytopenia may be an incidental findingon a routine blood test
-anemia thrombocytopenia, neutropenia
Diagnosis of CLL:
1. CBC: shows WBC of 50-200,000
2. Anemia, thrombocytopenia, and neutropenia common
3. Peripheral blood smear
a. Absolute lymphocytosis -almsot ALL of the WBCs are mature, small lymphocytes
b. Small smudge cells - leukemic cells that are "beaten up" in the blood.
2. Bone marrow biopsy with the presnse of infiltrating leukumic cells in the marrow.
What are the clinical features of macrocytic anemia?
2. SOre tongue (stomatitis and glossitis)
3. neuropathy - can distinguish etween vitamin B12 deficiency and folate deficiency.
a. demyelination in posterior columns, in lateral corticospinal tracts and spinocerebellar trats that ultimately leads to a loss of position/virbatory sensation in lower extremities, ataxia and UMB signs like increased DTR, spasticity, weakness, babinski sigh
4 leads to urinary and fecal inontinence, impotence
5. leads to dementia
PERIPHERAL BLOOD SMEAR OF G6PD
2. BITE CELLS
3. HEINZ BODIES (after the removal of the Heinz bodies look as if they are/have had bites taken out of them. The bitten areas are secondary to phagocytosis of heinz bodies by splenic macrophages recognizing them as foreign).
-heinz bodies are abnormal hemoglobin precipatites within RBCs that are visible with special stains
4. Deficient NADPH formation on G6PD assay
5. Measurement of G6Pd is diagnostic!
How is thrombocytopenia diagnosed?
CBC - platelet count
-BLEEDING TIME, PROTHROMBIN TIME (PT), partial thromboplastic time (PTT)
-to determine cause, the following may be helpful:
-exmaination of peripheral blood smear or bone marrow biopsy
Name two low grade or INDOLENT NHL:
1. Small lymphocytic lymphoma - related to CLL, elderly pts, indolent course
2. Follicular, predominant small, cleaved cell lymphoma - most common form of NHL with age of 55; diffuse, large cell, t(14; 18), indolent, PAINLESS LAD
1. Platelet count
2. Bleeding time
What are the clinical features of waldenstoms macroglobulinemia?
4. Abnormal bleeding
5. Hyperviscosity syndrome (due to elevated IgM)
6. THere is no definitive cure - use chemo, and plasmapheresis for hyperviscosity syndromes - some retinal vessel dilation with resulting hemorrhage and possible blindness because of elevated IgM which is already very LARGE
A t-cell lymphoma of the skin that presents with eczematoid skin lesions that progress to generalized erythroderma with CRIBRIFORM SHAPED lymphcytes.
Mechanical heart valves can hemolyze RBCs and lead to HA but which cause?
Extrinsic factors (mecanical hemolysis - heart valves or MAHA)
What is the treatment for MM?
1. ONLY begin treatment when: hypercalcemia, bone pain, and spinal cord compression begins
2. Systematic chemotherapy is the intial treatment with alkylating agents
3. Radiation therapy - if no response to chemotherapy and if disabling pain is present
3. Transplantation - autologous peripheral blood stem cell transplantation is preferred of bone marrow transplant
Screening can identify asymptomatic carriers (SCT) for who ____ couseling SHOULD BE PROVIDED
Diagnosis of CML
1. Marked leukocytosis - WBC 50-2000L with left shift toward granulocytes
2. Small amt of blasts/promyelocytes
4. Peripheral smear - leukemic cells in the peripherl blood: myelocytes, metamyelocytes ,bands and semented forms
5. Decreased leukocyte alk phos activity.
6. BMB shows leukemic cells
How is AIHA diagnosed?
1. Direct coombs test
a. If RBCs are coated with IgG (positive direct Coombc test), then the diagnosis if warm AIHA
b. If RBCs are coated with complement along, then the diagnosis if cold AIHA
c. If there is a positive cold agglutinin titer, then the diagnosis is cold AIHA
d. Spherocytes may e present in warm HA
Historical findings to consider in patients with anemia
1. Family history of hemophilia, G6PD deficiency, thalassemia
2. Bleeding (melena, recent trauma/surgery, hematemesis)
3. Chronic illness (eg recent failure)
4. ALcoholism (folate/b12/iron deficiency)
Physcial injury to RBCs leads to the presnese of fragmented RBCs called SCHISTOCYTES or HELMET cells on the blood smear that can occurs in (TTP, DIC, and patients with prosthetic heart valves.
T or F
What is ristocetin?
The ristocetin-induced platelet aggregation (RIPA) is an ex vivo assay for live platelet function to aggregate with help of von Willebrand factor and exogenous antibiotic ristocetin added in a graded fashion used to diagnose von Willebrand disease. It is similar to the ristocetin cofactor activity but has the added benefit in that it can diagnose type 2B vWD and Bernard-Soulier syndrome because it uses patients live endogenous platelets, whereas Ristocetin Cofactor Assay tests function of only the VWF but not the platelets. Riscocetin cofactor assay uses platelet poor plasma (with VWF but no platelets) and adds ristocetin and exogenous formalin fixed platelets which can passively agglutinate (but not actively "aggregate", as they are dead).
In an unknown fashion, the antibiotic ristocetin causes von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb), so when ristocetin is added to normal blood, it causes agglutination of fixed platelets or initiates the initial agglutination phase of aggregation of live platelets. In von Willebrand disease, where von Willebrand factor is absent or defective, abnormal agglutination occurs:
In type 1 vWD: hypoactive agglutination occurs
In type 2A vWD: hypoactive agglutination occurs
In type 2B vWD: hyperactive agglutination occurs
In type 2M vWD: hypoactive agglutination occurs activity
In type 2N vWD: normal agglutination occurs
In type 3 vWD: no agglutination occurs
What is the pathophysiology behind that of vaso-occlusive crisis?
Obstruction of microcirculation by sickeled RBCs. This leads to ischemia in various organs, producing the characteristic "painful crises".
1. Painful crisis including BONE often the tibia, humerus, femur and can be bilateral. lasts 2-7 days
2. Hand-foot syndrome (dactylitis) painful swelling of dorsa of hands and feet seen in infancy and early childhood (4-6 months). FIRST MANIFESTATION OF SCDISEASE. Caused by avascular necrosis of the metacarpal and metatarsal bones.
3. ACUTE chest syndrome: due to repeated episodes of pulmonary infarctions; clinical presentation is similar to pneumonia and associated with chest pain repiratory disress and pulmonary infiltrates and hypoxia.
4. Avascular necrosis of joints most common in the hip with decreased blood supply to femoral head and shoulder and decreased blood supply to humeral head.
5. Priapism-erection due to vaso-occlusion, usually lasting between 30 minutes to 3 hours. treatment with NIFEDIPINE (also used in cases for prevention of vasospasm post MI) or a trial of hydralazine can prevent further episodes.
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