Pallor Koilonychia (spoon nails) Palmar creases Increased cardiac output/"flow" murmur Tachycardia Orthostatic hypotension Petechiae or purpura Jaundice Glossitis or angular chelitis Thyroid enlargement GI bleed Increased vibratory or position sense
What are 4 microcytic anemias? Which is the most common and leading cause of anemia worldwide?
TICS: Thalassemias Iron deficiency <---most common Chronic inflammatory block (Anemia of chronic disease) Sideroblastic anemia
What is the most frequent cause of iron deficiency?
What is a pathognomonic symptom of iron deficiency anemia?
Pica - Craving/chewing on things with no nutritional value - Ex: ice, clay
What are common lab/peripheral smear findings with iron deficiency anemia?
Low MCV Low Iron Low Ferritin Low % sat Low Retic count High TIBC High Transferrin Peripheral smear: Hypochromic RBCs, Tear drop cells, elliptocytes, anisocytosis [red cells are unequal size (high RDW)]
What is Ferritin indicate? What is TIBC?
Ferritin represents iron stores. Ferritin will be low with iron def. anemia because iron stores are low
TIBC is total iron binding capacity - a protein carries iron around in the blood. TIBC will be high with iron def. anemia because there is a low amount of iron to bind to TIBC
Ferritin of <____ is pathognomonic of iron deficiency?
What is the definitive test for iron deficiency anemia?
Bone marrow biopsy
How do you treat iron deficiency anemia? What increases iron aborption?
Oral Iron (Ferrous sulfate 325 PO TID) or Parenteral Iron. Ascorbic acid (Vit C) doubles absorption.
AE of Iron?
GI side effects: metallic taste, N/V/D, flatulence, constipation, epigastric distress Black/green or tarry stools
How long does it take to correct iron def. anemia with iron supplementation? How long should it be continued?
6 weeks. 6 months after renewal of stores. Test of choice to measure progress is retic count.
Clinical features of iron overdose?
Iron causes localized necrosis and hemorrhage at the point of contact in the GI system resulting in abdominal pain, vomiting, bloody diarrhea, and hematemesis.
What is thalassemia?
Group of hereditary disorders characterized by decreased of absent synthesis of alpha or beta globin chains
How are thalassemias categorized?
Type: A (alpha chain is affected) or B (beta chain is affected) Severity
What are the three levels of severity with thalassemia?
Trait - no clinical impact Intermedia - there are RBC tranfusion requirements Major - Life threatening
Clinical features of alpha thalassemia?
A mutation that deletes one or more of the a-chain genes on chromosome 16 Clinically milder than beta thalassemia More common in Asians
Clinical features of beta thalassemia?
Caused by a point mutation 2 types More common in Mediterranean and African populations More severe disease and presents early in life (6 months)
What are the 2 types of beta thalassemia and clinical features of each?
Minor: Increased level of HgA2, Target cells.
Major (AKA Cooley's anemia): More severe. Increased level of HgbF.
Labs/peripheral smear findings for thalassemias?
Low MCV Normal Iron Normal TIBC Normal % sat Normal ferritin Abnormal Hgb electrophoresis Elevated LDH Peripheral smear: Elliptocytes, Target cells
Best test for diagnosing thalassemias?
How do you treat thalassemias?
If mild: Genetic counseling and education (avoid iron)
If severe: Folate Transfusions Iron chelation therapy Bone marrow/stem cell transplant Splenectomy
What are common causes of anemia of chronic disease (ACD)?
Secondary to... Chronic infection Inflammation Cancer Liver disease ESRD
Labs/peripheral smear findings for ACD?
Can be microcytic or normocytic Low Iron High Ferritin Low Transferrin
How do you treat ACD?
Treat underlying cause Give EPO
What is Sideroblastic anemia?
Anemia due to mitochondrial defect which prevents the incorporation of iron in to hemoglobin. Iron accumulates in the mitochondria and forms a "ringed sideroblast"
Causes of sideroblastic anemia?
What are causes of acquired sideroblastic anemia? What is MC?
Excessive alcohol use <---MC B6 (pyridoxine) deficiency Lead poisoning Copper deficiency
Lab/peripheral smear findings with sideroblastic anemia?
Low MCV in hereditary High MCV in acquired High Ferritin High Iron Low TIBC Ringed sideroblasts are seen
Pernicious anemia - lack of intrinsic factor due to a hereditary autoimmune disease that usually doesn't present until after age 35
What are hallmark clinical features of B12 deficiency?
Beefy, red tongue Glossitis Neurologic symptoms (stocking glove paresthesias, loss of position, fine touch, and vibratory sense, ataxia)
What is the pathognomonic finding of lead toxicity?
What are common lab findings with B12 deficiency?
High MCV Low B12 Anisocytosis and poikilocytosis Pancytopenia Increased LDH Mildly increased Bilirubin HIGH Homocysteine and Methylmalonic acid (MMA) levels Hypersegmented Neutrophils
How do you treat B12 deficiency?
1mg B12 IM injections - if due to malnutrition Oral therapy - if due to decreased intake (vegetarians)
What could happen if B12 deficiency goes on for too long?
Irreversible dementia and neurologic symptoms (note neuro deficits are reversible if treated within 6 months)
What does folic acid (B9) do in the body and where is it found?
Cellular reactions, DNA synthesis Found in fruits, vegetables, cereals, bread
What is the most common cause of folate deficiency?
Inadequate dietary intake or to increased use, such as in pregnancy
Hallmark findings with folic acid deficiency?
Glossitis NO NEURO SX Vague GI symptoms
What are lab findings with folic acid deficiency?
High MCV HOWELL-JOLLY bodies (nuclear DNA remnants) Normal B12 Low Folic Acid High Homocysteine LOW-normal MMA! Oval macrocytic RBCs Hypersegmented Neutrophils
Tx for folic acid deficiency?
1mg/day of folic acid Avoid alcohol and certain meds
What is important to r/o when treated folic acid deficiency?
Normocytic normochromic anemias
ACD Hemolytic anemias Anemia of hemorrhage Aplastic anemia
What is Aplastic anemia?
A decrease in production of all cell lines due to damage to stem cells
Causes of aplastic anemia?
What is the MC form of hereditary aplastic anemia?
Fanconi anemia. Affects children Characterized by pancytopenia with macrocytic anemia and congenital malformations (short stature, hypopigmented spots and café-au-lait spots, abnormality of thumbs, microcephaly or hydrocephaly, hypogonadism, and developmental delay)
What are the characteristic lab findings in aplastic anemia?
Pancytopenia and a hypocellular bone marrow
Treatment of aplastic anemia?
Bone marrow transplant
What are the hemolytic anemias?
Sickle Cell disease (SCD) G6PD deficiency Hereditary Spherocytosis Polycythemia vera
What is hemolysis?
Premature destruction of RBCs in the reticuloendothelial system or in the blood vessels. Bilirubin will be elevated from break down of RBCs
What does chronic hemolytic anemia lead to?
Jaundice due to increase in indirect bilirubin Pigment gallstones Splenomegaly Poorly healing ulcers over tibia Petechiae and purpura
What are common lab findings for all hemolytic anemias?
Haptoglobin is depressed High indirect and total bilirubin Elevated LDH Elevated retic count Falling Hgb Peripheral smear will show SHISTOCYTES
What serum blood test helps determine the degree of hemolysis?
Haptoglobin - decreased with inherited hemolytic anemias
Which type of Coombs test would you do to evaluate hemolytic anemia?
Direct - Mix the patient's RBC with a reagent and look for IgG and C3
What is Polycythemia vera?
Disorder of the bone marrow which causes too many RBCs (HCT > 60%) to be produced. The numbers of WBCs and platelets may also be higher than normal. Rare. M>F
What causes polycythemia vera?
Clinical features of polycythemia vera?
HA Dizziness Tinnitus, blurred vision, fatigue Epistaxis (due to mucosal engorgement and platelet dysfunction) Erythromelalgia (burning pain in feet or hands with erythema, pallor, and cyanosis) PRURITIS following warm showers
Serial phlebotomy Hydroxyurea, aspirin, allopurinol
Complications from polycythemia vera?
Thrombosis <---MC Transformation to acute myelogenous leukemia (AML)
What is Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency)?
Hereditary disorder which is X linked and most commonly seen in AA males. It is the MC disease-producing enzymopathy in humans. There are more than 300 variants of the disease and some protection against malaria which likely contributes to its high frequency in the population. Oxidative stress causes hemolysis.
What does G6PD do?
Catalyzes two important reactions: the oxidation of G6P and also the reduction of NADP+ to NADPH. NADPH is a required co-factor in many enzymatic reactions in the body. In red cells, NADPH protects the cells against oxidative stress and therefore is heavily reliant on G6PD. In the presence of oxidative stress and oxidative pharmacologic agents, red blood cells begin to rapidly hemolyze.
What are causes of oxidative stress that lead to hemolysis in G6PD deficiency?
How do patients present with acute hemolytic crisis?
Jaundice Anemia Splenomegaly Vascular collapse
What lab findings will you see with G6PD?
HEINZ bodies - denatured Hgb BITE CELLS - look like a bite has been taken out of them High retic count High indirect bilirubin Low G6PD levels Low Hematocrit Decreased haptoglobin
How do you treat G6PD?
Self-limiting. Pts are usually asymptomatic in between attacks. Avoid oxidative drugs and food
What is hereditary spherocytosis?
Hereditary disorder of the RBC membrane scaffolding proteins (actin or spectin) which leads to chronic hemolytic anemia.
What does the defect do to the morphology of the RBC?
Causes it to become spherical (spherocyte) which is less deformable and unable to squeeze through capillaries and they hemolyze
How do patients with hereditary spherocytosis present?
+ family history May or may not have anemia Splenomegaly Chronic hemolysis which causes jaundice and gallstones
What test confirms the presence of spherocytes?
Osmotic fragility test - involves incubating red blood cells in hypotonic saline in increasing dilutions. This causes the red blood cells to swell and eventually burst. The spherocytes more readily lyse than normal cells in hypotonic solutions. Not a specific test however.
What lab findings will you see with hereditary spherocytsosis?
SPHEROCYTES High Retic count Increased MCHC Microcytic, hyperchromic cells Increased indirect bilirubin Negative Coombs test
Children with hereditary spherocytosis are at risk for aplastic crisis as result of an infection from which virus?
How do you treat hereditary splenocytosis?
TOC: Splenectomy Folic acid supplementation
What is sickle cell disease (SCD)?
Autosomal recessive disorder where abnormal hemoglobin leads to chronic hemolytic anemia and microvascular occlusion
What are the hallmarks of SCD? (4)
Recurrent painful episodes Positive family history Irreversibly sickled cells Hemoglobin S seen on electrophoresis
What causes increased sickling?
Concentration of Hgb S and presence of other Hgb in cell Hypoxemia Acidosis Dehydration
Where is the pain of SCD normally felt?
Long bones Back Chest
Repeated vascular occlusions damages which organs?
Hct is 20-30% Sickled cells on smear Howell-Jolly bodies WBC elevated May have thrombocytosis Elevated indirect bilirubin
What is the diagnostic study of choice for SCD?
How do you treat SCD?
Prevention of infection - vaccinate! Prevention of vaso-occlusive crises - HYDROXYUREA
MOA of Hydroxurea?
Increases fetal hemoglobin (HbF) production and slightly raises the total hemoglobin concentration in the body. Fetal hemoglobin reduces the chance that RBCs will sickle.
How do you treat SCD crisis?
Treat underlying cause Hydrate Oxygen Transfusion Analgesia
Aplastic crisis: ↓ Hb + reticulocytopenia, parvovirus B19 Acute chest syndrome: Fever, CP, CXR: pulmonary infiltrate (MC cause of death in adults) Splenic sequestration crisis: rapid splenic sequestration of RBCs → splenomegaly + severe anemia Stroke Aseptic necrosis of the femoral head Dysfunctional spleen → ↑ infection risk Salmonella osteomyelitis S. pneumoniae sepsis: MC cause of death in children
What treatments can help prevent stroke in SCD patients?
Von Willebrand disease Hemophilia A Hemophilia B Coagulopathy of liver disease Vitamin K deficiency Factor V Leiden Cancer as a cause of coagulopathy DIC VTE/DVT/PE
What is the most common inherited bleeding disorder?
von Willebrand Disease
What is von Willebrand factor (vWF)? What does it do?
A large glycoprotein that aggregates platelets and prolongs the half life of factor VIII
What are the two major types of VWD?
Type 1: Patients have a quantitative abnormality of vWF Type 2: Patients have a qualitative abnormality of vWF
How does Type 1 VWD present?
Mild to moderate platelet type bleeding (MUCOSAL membranes - epistaxis, gingival bleeding)
What are lab findings of Type 1 VWD?
VWF activity and Ag are mildly depressed
How does Type 2 VWD present?
Moderate to severe bleeding that presents in childhood
What are lab findings of Type 2 VWD?
Ag:vWF activity is 2:1 So they have lots of factor but it doesn't work
How do you treat VWD?
DDAVP for Type 1 Factor VIII replacement if more severe
What is Hemophilia A?
Deficiency of Factor VIII X-linked recessive disorder - which means only males will get disease and females will be carriers Most severe bleeding disorder. 2nd most common after VWD.
How do patients with Hemophilia clinically present?
If mild: spontaneous bleeding may occur with trauma or surgery
If severe: spontaneous bleeding into joints and soft tissues (hemarthrosis), epistaxis, intracranial bleeding, melena, gingival bleeding
Where is the MC site of spontaneous hemarthrosis in adults? Children?
Adults: Knee Children: Ankle
What lab findings will you see with hemophilia A?
Low factor VIII activity Prolonged aPTT that corrects when mixed with normal plasma
Tx for Hemophilia A?
Factor VIII replacement DDAVP Avoidance of ASA
What is Hemophilia B?
AKA Christmas disease Deficiency of Factor IX X-linked recessive disorder Less common than Hemophilia A
Tx for Hemophilia B?
Replace Factor IX
What is the most common acquired coagulopathy?
Vitamin K deficiency - due to poor diet, liver failure, malabsorption, certain drugs
How do you treat Vit K deficiency?
Oral or parenteral Vit K FFP Green leafy veggies
What is thrombocytopenia?
<150,000 Severe is <50K
How do you determine the cause of thrombocytopenia?
Bone marrow biopsy
What are 6 major acute thrombocytopenias?
ITP TTP HIT HUS HELLP DIC
What is Immune Thrombocytopenic Purpura (ITP)
Self limited autoimmune (IgG) condition where pathogenic antibodies bind to platelets and result in accelerated platelet clearance. Idiopathic cause and also associated with connective tissue disorders, lymphoma, meds, infections, viruses (in children)
Clinical features of ITP?
Sudden appearance of a petechial rash, bruising, or bleeding in an otherwise healthy child with a history of recent viral infection Cutaneous bleeding (petechiae, purpura, or bruising) is the MC finding (seen in 85% of cases)
Diagnosis of ITP?
The diagnosis of ITP is based upon the following criteria: Platelet count < 100,000/microL with otherwise normal CBC Normal peripheral blood smear
Tx of ITP?
Usually resolves on its own within 3 mo Sometimes requires steroids, IVIG, or splenectomy
What is Thrombotic thrombocytopenia Purpura (TTP)
Thrombocytopenia due to platelets making small clots in the microvasculature and microangiopathic hemolytic anemia (RBCs are exploding). Can be congenital or acquired. Due to inhibition of the enzyme ADAMTS13, which leads to large multimers of von Willebrand factor
HUS doesn't have neuro abnormalities or fever. HUS occurs in children after an E.coli infection TTP occurs in more commonly in adults
What will be seen on peripheral smear with TTP
Schistocytes (fragmented erythrocytes, also called helmet cells)
How do you treat TTP?
Goal: Remove antibody and replenish cleaving protease activity Best treatment: Plasmaphoresis (remove plasma and replace with fresh frozen plasma) for 1-8 weeks Steroids and anti-platelets
What do you not want to do when treating TTP?
Give platelets - causes more clotting
Factor V Leiden Prothrombin mutation Hyperhomocysteinemia Protein C def Protein S def Antithrombin III def
When should you suspect an inherited hypercoagulable state?
In patients with venous or arterial thrombosis at a young age or unusual locations, recurrent thromboses or pregnancy losses, or +FHx
What is leukopenia?
Low number of circulating WBCs (<4.5K) in the bloodstream. Caused by infections, toxins, meds, chemo, leukemias, myelomas, or primary marrow failure.
What are clinical features of leukopenia?
Fever/chills Opportunistic infections Signs of malignancy
What is leukemia?
Increased production of abnormal leukocytes and leukocyte precursors in circulation and bone marrow. Four types: AML, ALL, CML, CLL)
How are leukemias classified?
Cell type (myelocytic - ML or lymphocytic LL) Acute vs chronic
What is the most common leukemia?
What is the most common leukemia in children?
What is acute leukemia?
Immature, abnormal cells are in the bone marrow (>20%) and peripheral blood (>10%) and frequently in the liver, spleen, lymph nodes, and other organs. Symptoms occur over days.
What are clinical features of acute leukemias?
Symptoms are related to replacement of normal bone marrow with abnormal WBCs, all cell lines will be affected: Gingival bleeding Epistaxis Menorrhagia Infections Fatigue, fever, lethargy, headache, bone/joint pain
Diagnostic studies and findings for acute leukemias?
CBC - will show pancytopenia with blasts Uric acid - Hyperuricemia Cytogenic studies
What is acute lymphocytic leukemia (ALL)?
Leukemia that primarily affects CHILDREN (80% are 3-7). 75% affects B-cell precursors 20% T-cell precursors MOST CURABLE type of leukemia
What are symptoms specific for ALL?
Lymphadenopathy and hepatosplenomegaly
Diagnostic hallmark for ALL?
Terminal deoxynucleotidyl transferase
How do you treat ALL?
Aggressive chemo for 2 years Consider bone marrow transplant
What indicates a poorer prognostic factor for ALL?
Presence of Philadelphia chromosome
Tx for hypercoagulable states?
Usually asymptomatic Consider prophylactic anticoagulation if risk factors develop
What is acute myelogenous leukemia (AML)?
Acute leukemia that primarily affects adults (mean age is 60). There is excessive proliferation myeloid precursors cells.
What are myeloblasts?
Immature hematopoietic cells with large nuclei and prominent nucleoli that can develop into basophils, eosinophils and neutrophils.
Diagnostic hallmark for AML?
Auer Rods - pinkish-red rod-like structures in the cytoplasm of myeloblasts
What jagged, irregularly shaped, red blood cells indicate disseminated intravascular coagulation, a complication of acute myelogenous leukemia?
PHILADELPHIA CHROMOSOME or BCR-ABL gene LEUKOCYTOSIS (WBC count >150) Peripheral smear will show anemia and thrombocytosis
What is standard pharm tx for CML? Curative tx?
Bone marrow transplant <---curative Chemo - Imatinib (Gleevec) is standard therapy
What is Lymphoma?
A group of blood cell tumors that develop from lymphatic cells.
What are two major lymphomas?
Hodgkin disease (HD) Non-Hodgkin lymphoma (NHL)
What is Hodgkin disease?
Group of cancers characterized by enlargement of lymphoid tissue, spleen, liver, and presence of REED-STERNBERG cells (bi-lobed nuclei). Associated with EBV MC between 15-45 yo
What is the MC presentation of Hodgkin disease?
Painless mass in the neck
What are clinical features of Hodgkin disease?
Painless cervical, supraclavicular, and mediastinal lymphadenopathy May have painful lymph nodes after ingestion of alcohol Constitutional B symptoms: Fever, night sweats, weight loss SOB
Diagnostic studies for Hodgkin disease?
Lymph node biopsy - will show REED STERNBERG CELLS PET scan CT of neck, chest, abdomen, pelvis for staging
Tx for Hodgkin disease?
Chemo cures most - Adriamycin, bleomycin, vinblastein, dacarbazine (ABVD) Radiation <--- TOC for low risk stages If a young patient, consider sperm banking for fertility preservation If relapse occurs, consider high dose chemo with stem cell transplant
What is Non-Hodgkin Lymphoma (NHL)?
Lymphoma where 90% is from B lymphocytes Higher incidence in patients who are immunodeficient Peak incidence between 20-40
What are clinical features of NHL?
Diffuse, painless, persistent lymphadenopathy Extranodal involvement Associated with EBV B symptoms (in intermediate and high grade disease)
Diagnostic studies for NHL?
Lymph node biopsy PET CT
How do you treat NHL?
Dependent on specific type and grade Range of options: can either monitor or aggressively treat with chemo Tumor lysis prophylaxis Bone marrow transplant
What criteria is used to stage Hodgkin and non-Hodgkin lymphoma?
The Ann Arbor System
What is Multiple Myeloma?
Malignancy of plasma cells (proteins), which produce an abundance of monoclonal paraprotein (M protein). Unknown cause. Median age of diagnosis is 65.
What are plasma cells?
Cells in the bone marrow that are differentiated B cells. They produce antibodies to fight infection. In MM they crowd out other cells in the bone marrow
What are clinical features of MM?
CRAB: HyperCalcemia Renal disease Anemia (pancytopenia) Bone pain (Osteolysis with bone pain, Osteoporosis, Pathologic fractures)
Recurrent infections Paraprotein levels are increased
Diagnostic findings with MM?
Anemia with normal cell morphology ROULEAUX FORMATION (RBCs that stacked like coins) MONOCLONAL SPIKE on serum electrophoresis BENCE JONES PROTEIN in urine Lytic lesions on Xray of skeleton BMP: Hypercalcemia, increased serum protein Renal failure
What is the classic triad of MM?
Plasmacytosis Bone lytic lesions M-protein in serum/urine
How do you manage MM?
Chemo Radiation Bone marrow transplant Hypercalcemia treatment
UA Pathophysiology (Lachel Story) Ch. 3 - Hematopoietic Function38 terms