Pathoma Chapter 4 Hemostasis
Terms in this set (71)
Primary hemostasis ____.
Secondary hemostasis ____.
forms weak platelet plug and is mediated by interaction btwn platelets and vessel wall.
stabilizes the platelet plug and is mediated by the coagulation cascade.
What is the very first step in primary hemostasis?
Transient vasoconstriction, mediated by neuronal reflexes and
release from endothelial cells
Step 2, primary hemo:
Platelets bind vWF via the __ receptor. Platelets adhere to each other via the __ receptor
Where are the two places vWF comes from?
W-P bodies of endothelial cells and alpha-granules of platelets
Step 3, primary hemo:
Adhesion induces shape change in platelets and degranulation w release of multiple mediators
Two mediators are released from platelets during platelet degranulation. What are they and what do they do?
ADP - promotes expression of GPIIb/IIIa
TXA2 - promotes platelet aggregation, synthesized by
The early platelet plug uses __ as a linking molecule
Disorders of primary hemostasis-
-mucosal bleeding (
), hemoptysis, GI bleeding, hematuria, and menorrhagia
-intracranial bleeding with severe thrombocytopenia
Sizes of skin bleeding:
Petechiae are a sign of
Immune thrombocytopenia purpura (ITP):
What type of hypersensitivity?
Autoimmune (IgG) response to platelet antigens (ex: GPIIb/IIIa)- Abs produced by plasma cells in spleen
Acute: children, weeks after viral infection or immunization, self-limited
Chronic: Adults, primary or secondary to SLE, etc. Can cause thrombocytopenia in fetus (IgG)
Type II (antibody coated cells)
What is the most common cause of thrombocytopenia in children and adults?
Labs for ITP-
dec platelet count
inc megakaryocytes on bone marrow biopsy
Tx for ITP?
IVIG can raise platelet count- short lived
Why do you do splenectomy for ITP patients?
The antibody-bound platelets are eaten by splenic macrophages - no spleen, no eating
Microangiopathic hemolytic anemia
2ndary to these 2 disorders
Platelet microthrombi in small vessels, consumes platelets, shears RBCs
Hemolytic anemia with
HUS and TTP
Decrease in ADAMTS13 (norm cleaves vWF) -> platelet aggregation
Usually due to acquired autoantibody against ADAMTS13, adult female
Common causative organism
Thrombi of kidney vessels due to endothelial damage by drugs or infection
E. coli O157:H7 verotoxin
(undercooked beef)-> hemolysis -> shistocytes
TTP thrombi usually involve vessels of the __
HUS thrombi usually involve vessels of the __
Labs for Microangiopathic hemolytic anemia:
Thrombocytopenia w inc bleeding time
normal PT/PTT (haven't activated cascade)
anemia with schistocytes
inc megakaryocytes on bone marrow biopsy (bone marrow producing extra platelets)
Tx for Microangiopathic hemolytic anemia
plasmapheresis and corticosteriods, particularly in TTP
Bernard-Soulier deficiency __
Glanzmann thrombasthenia deficiency __
Why do we use the acronym Big Suckers for Bernard-Soulier deficiency?
GPIb deficient platelets don't live as long
The marrow sends out more immature RBCs,
What is Glanzmann thrombasthenia?
Genetic GIIb/IIIa deficiency; platelet aggregation is impared
ASA effects on platelets?
irreversibly inactivates COX; lack of TXA2 impairs aggregation
How does stabilization of the weak platelet plug take place in secondary hemostasis?
Coagulation cascade generates thrombin, which converts fibrinogen to fibrin, the fibrin then cross-links
Clinical features of disorders of secondary hemostasis?
deep tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures (circumcision and wisdom tooth extraction)
What is the activating substance for the extrinsic and intrinsic pathways? (include the initiating Factor)
Extrinsic - factor VII - tissue thromboplastin (PT)
Intrinsic - factor XII - subendothelial collagen (PTT)
Factors are produced inactively. Besides the specific activating substances (tissue thromboplastin/subendothelial collagen), what else is needed for activation?
Phospholipid surface of platelets
PT measures factors:
PTT measures factors:
VII and common (2, 5, 10, fibrinogen)
XII, XI, IX, and common (2, 5, 10, fibrinogen)
-Factor 8, X linked Rec
-deep tissue, joint, and post surgical bleeding
-inc PTT, normal PT, dec Factor 8, normal platelet count and bleeding time
-recombinant factor 8
What is hemophilia B?
same as Hemo A except with
What is the difference between coagulation factor inhibitor and a hemophilia? As in, how would you distinguish the two?
In CFI, PTT does NOT correct upon mixing normal plasma with patients, because it is antibody mediated, unlike hemophilias which are genetic deficiencies of factors and will correct upon mixing study
This factor is stabilized by vWF, it is also deficient in vWF deficiency __.
What will the PT/PTT tests show?
What is the function of this factor?
PTT inc. (intrinsic pathway), inc bleeding time
It is a cofactor for IXa for converting X to Xa
What hemostatic disorder will have an abnormal ristocetin test, and why?
Ristocetin induces platelet aggregation by causing vWF to bind GPIb
What is the treatment for vWF deficiency? How does it work?
ADH analog, increases vWF release from W-P bodies of endothelial cells
Vit K deficiency-
activated by epoxide reductase in liver -> carboxylates factors 2,7,9,10 and proteins C and S
Newborns, long term abx therapy, malabsorbtion
How does heparin-induced thrombocytopenia happen?
Heparin complexes with factor IV
IgG antibodies are developed which destroy platelets (by the spleen)
The fragments of the destroyed platelets activate the remaining platelets, leading to thrombosis
What is DIC?
pathologic activation of coagulation cascade
widespread microthrombi result in ischemia and infarction
consumption of platelets and factors results in bleeding, esp from IV sites and mucosal surface
Why does adenocarcinoma cause DIC?
Mucin activates coagulation
Why can DIC arise in an obstetrics setting?
Tissue thromboplastin in amniotic fluid activates coagulation
What kind of leukemia/lymphoma can cause DIC?
APML - primary granules activate coagulation
What kind of complication would you worry about in a rattlesnake bite?
Lab findings for DIC?
dec platelet count
microangiopathic hemolytic anemia-> shistocytes
elevated fibrin split products (D dimer)
What is the best screening test for DIC?
Tells you that the whole cascade has been activated, all the way down to fibrin splitting
What converts plasminogen to plasmin? Plasmin does these 3 things.
What inactivates plasmin?
Cleaves fibrin AND serum fibrinogen
Destroys coag. factors
Blocks platelet aggregation
Why would a radical prostatectomy cause plasmin overactivity?
Why would cirrhosis of the liver?
Releases urokinase, which activates plasmin (this will cause excessive cleavage of fibrinogen)
Reduced production of a2-antiplasmin
Why won't you see D-dimer formation in plasmin overactivity?
Lyses serum fibrinogen - D-dimers aren't produced because fibrin thrombi don't form
What is the treatment for plasmin overactivity?
aminocaproic acid - block plasminogen activation
What are lines of Zahn and where are they found?
Alternating layers of platelets/fibrin and RBCs, attached to vessel wall
found in thrombi
What is Virchow's Triad?
-risk factors for thrombosis
Disruption in blood flow
Endothelial cell damage
What are some substances from endothelial cells that prevent thrombosis?
thrombomodulin (redirects thrombin to activate protein C, which inactivates factors V and VIII)
What can cause disruption of normal blood flow?
immobilization, cardiac wall dysfunction, aneurism
--> stasis and turbulence ->thrombosis
Endothelial cell damage-
protective functions of endo cells?
disrupts protective function of endothelial cells, inc risk for thrombosis
-block exposure to subendothelial collagen and underlying tissue factor
-vasodilation and inhib of platelet aggregation
-secrete heparin-like molecules-augment ATIII, which inact thrombin and coag factors
What does thrombomodulin do?
redirects thrombin to activate Protein C, which inactivates factors V and VIII
Causes of endothelial damage?
high levels of homocysteine
Why can B12/folate deficiency increase risk for thrombosis?
B12 and folate participate in transfer of a methyl group to cobalamin (B12) and then to homocysteine -> methionine. Buildup of homocysteine causes endothelial cell damage
Cystathione beta synthase (CBS) deficiency
Characteristics of affected individuals
CBS converts homocysteine to cystathionine - lack of CBS would lead to homocysteine buildup and thrombosis risk
Characterized by vessel thrombosis, mental retardation, lens dislocation, long slender fingers, homocysteinuria
What is a hypercoagulable state?
due to excessive procoag proteins or defective anticoag proteins
recurrrent DVTs at a young age
What is the normal role of Protein C and S?
effects of a deficiency?
normally inactivating factors V and VIII
decreases neg feedback on coagulation cascade; inc risk for warfarin skin necrosis
When starting warfarin, why must you also have heparin running also?
Effects in preexisting C or S deficiency?
warfarin blocks epoxide reductase in liver-> can't activate Vit K -> C, S, and 2,7,9,and 10 dont function
Proteins C+S have shorter 1/2 life relative to 2, 7, 9, 10 -> so inc risk for thrombus
a C or S deficiency (autosomal d) -> greatly inc risk for thrombus-> Warfarin skin necrosis
Factor V Leiden
Mutated factor V that can't be cleaved by C or S -> can't be shut off
Most common inherited hypercoagulable state
Inherited pt mutation in prothrombin that results in increased expression
Increased prothrombin = more thrombin -> thrombus formation
What is ATIII normally activated by?
normally ATIII inactivates coagulation factors and thrombin
def dec protective effects of hep-like molecules-> inc risk for thrombus
Activated by heparin and heparin-like molecules
Labs for ATIII deficiency?
rise with standard hep dosing- bc hep act ATIII which isn't there
what do you think when you see a
in an embolus?
What is a fat embolus?
asso with bone fractures, often while fracture is present or shortly after repair
CM- dyspnea and petechiae on skin overlying chest
What is caisson disease?
Chronic form of gas emboli - caused by multifocal ischemic necrosis of bone
-seen as joint and muscle pain and resp symptoms
How will an amniotic fluid embolus present?
SOB, neuro sx, DIC (thrombogenic nature of amniotic fluid);
-usually during labor
Will see squamous cells and keratin debris, usually in lungs
-usually thromboembolis, often DVT of lower extremity, often femoral, iliac or popliteal veins
--> pulm infarction if large or med size vessel obstructed in pts with preexisting cardiopulm compromise
What are some tests to order if PE/DVT is suspected?
D-dimer (will be elevated)
Spiral CT shows vascular filling defect in lung
Doppler US is useful for lower extremity DVT
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