Hemostasis II Flashcards
What are weibel palade bodies?
vessicular bodies released by endothelial cells after damage to a vessel wall
- they include von Willibrand Factor as well as P-selectin
–> will activate both clotting and margination of PMNs
What are the 4 steps of Primary Hemostasis?
- *1. Transient constriction of damaged vessel**
- mediated by reflex neural stimulation and endothelin released from endothelial cells
- *2. Platelet adhesion to surface of disrupted vessel**
- vWF (released by endothelial cells and platelets) binds exposed subendothelial collagen
- platelets bind vWF using GPIb receptor
- *3. Platelet degranulation**
- adhesion induces shape change and degranulation
- ADP (dense granules) promotes exposure of GPIIb/IIIa receptor on platelets
- TXA2 promotes platelet aggregation
- *4. Platelet Aggregation**
- Platelets aggregate via GpIIb/IIIa using fibrinogen as linking molecule
- results in platelet plug
What are symptoms of primary hemostasis disorders?
Primary hemostasis disorders are caused by either thrombocytopenia or non-functional thrombocytes
Results in:
Petechiae*, purpura, ecchymoses
Easy Bruising
Mucosal bleeding
*Petechiae are sign of thrombocytopenia and are not usually seen with qualitative disorders
What causes TTP?
Decreased ADAMTS13
- ADAMTS13 normally cleaves vWF mlutimers into smaller monomers for evenutal degredation
- leaving uncleaved, multimers leads to abnormal platelet adhesion, resulting in microthrombi
What are clinical findings of TTP and HUS?
Skin and mucosal bleeding (platelets consumed in platelet microthrombi)
** Microangiopathic hemolytic anemia** (platelet microthrombi shear RBCs in kidney and CNS)
Fever
renal insufficiency (predominant in HUS)
CNS abnormalities (predominant in TTP)
Thrombocytopenia
Increased bleeding time
Normal PT/PTT
Anemia with schistocytes
Increased megakaryocytes on BM biopsy
What is Bernard-Soulier syndrome?
Genetic GPIb deficiency: platelet adhesion is impaired
- Mild thrombocytopenia with enlarged plateletes (Big Suckers = Bernard-Soulier)
What is Glanzmann thromblasthenia?
Genetic GIIb/IIIa deficency: platelet aggregation impaired (no primary hemostasis)
How does aspirin affect bleeding time?
Aspirin irreversibly inactivates COX1/2
- Results in a lack of TXA2, which then impairs platelet aggregation (TXA2 is chemical messenger to bring in other platelets)
What is the process of secondary hemostasis?
- Coagulation cascade produces thrombin
- thrombin cleaves fibrinogen into fibrin, which is then cleaved and cross-linked
–> end product is: a stable Platelet-fibrin thrombus
What is necessary for the activation of the coagulation factors?
- Exposure to an activating substance
- Phospholipid surface (platelets)
- Calcium
What does the PT and PTT measure, respectively?
PT = extrinsic
(You do PT outside)
PTT = intrinsic
What is hemophilia A?
Genetic Factor VIII deficiency
- X-linked recessive; predominanty affects males
- Can arise form new mutation without family history!
What are signs and symptoms of hemophilia A?
Deep tissue, joint and post-surgical bleeding
Increased PTT, Normal PT
Decreased Factor VIII
Normal platelet count and bleeding time
What is hemophilia B?
Genetic Factor IX deficiency (Christmas factor deficiency)
- Resembles hemophilia A, except Factor IX levels are decreasd instead of Factor VIII
What is the most common coagulation factor inhibitor?
Anti-factor VIII
What are signs and symptoms of vWF deficiency?
Note: most common type is autosomal dominant with decreased vWF
Decreased ability for platelets to adhese to damaged vessel using GPIb
- Mild mucosal and skin bleeding
- Increased bleeding time
- Increased PTT (need vWF to stabilized factor VIII), normal PT
- Abnormal ristocetin test
What is treatment for vWF deficiency?
Desmopressin
- Increases release of vWF from Weibel-Palade bodies of endothelial cells
Vitamin K deficiency affects what coagulation factors?
II (thrombin), VII, IX, and X
(Vit. K required to gamma-carboxylate these factors)
How does Vitamin K deficiency occur?
Vitamin K is produced by bacteria in our gut
Deficiencies occur in:
Newborns
Long-term antibiotic therapy
Malabsorption
Why does liver failure result in bleeding disorders?
Decreased production of coagulation factors
Decreased activation of vitamin K by epoxide reductase (therefore, no activation of II, VII, IX, and X)
Effect of liver failure on coagulation is followed using PT (Factor VII has shortest half-life)
What is HIT?
Heparin Induced Thrombocytopenia
- Platelet destruction that arises secondary to heparin therapy
- Heparin forms complex with Platelet Factor 4
Patient then develops IgG antibodies to this complex resutling in destruction of platelets - Fragments of destroyed platelets may activate remaining platelets, leading to thrombosis
How is HIT treated?
Stop Heparin and a different anticoagulant (NOT coumadin = these patients are at increased risk of coumadin skin necrosis)
What is DIC?
Disseminated Intravascular Coagulation
- Pathologic activation of coagulation cascade
- Widespread microthrombi result in ischemia and infarction
- Consumption of platelets and factors results in bleeding, especially from IV sites and mucosal surface (mouth, lung, GI tract, kidneys, etc)
- *Almost always secondary to another disease process:**
- Obstetric complication (amniotic fluid)
- Sepsis
- Adenocarcinoma
- Acute promyelocytic leukemia (by release of Auer rods)
- Rattlesnake bite
What are the laboratory findings of DIC?
Decreased platelet count
Increased PT/PTT
Decreased fibrinogen
Microangiopathic hemolytic anemia
Elevated fibrin split products (D-dimer)
