Flashcards in Hemostasis: Approach to Patient (complete) Deck (29):
What are the events occurring during primary hemostasis?
- Aggregation of platelets
forms a platelet plug
What are the events occurring during secondary hemostasis?
- Formation of fibrin network (generated by coag cascade)
Stabilizes the platelet plug
Describe the structure of a mature platelet. Include dense granules, alpha granules, and phospholipids
- No nucleus, but they have mitos
- Three kinds of granules: dense, alpha, lysosomal
- Phospholipid membrane
What do dense granules contain?
What do alpha granules contain?
Proteins essential for platelet function:
- procoag proteins (fibrinogen, Factor 5, vWF)
- platelet factors for activation
- growth factors
What do lysosomal granules contain?
What are the 3 functions of platelets?
1) Adhesion to vascular subendothelium at injury sites
2) Activation of intracellular signaling pathways
3) Platelet aggregation to form the platelet plug
Describe the process of platelet adhesion. Include subendothelial collagen, von Willebrand factor, and glycoprotein 1b.
- w/ injury, subendo components exposed => vWF adheres to this
- circulating platelets adhere to exposed subendo via interaction w/ GP1b
- GP3 and 4 also interact w/ exposed subendo (collagen) => ligands form
LEADS TO: firm adherence of the platelet to subendo surface
Explain why platelet adhesion to blood vessels does not occur under normal circumstances
- Only happens when subendothelium is exposed
- Can only happen during vessel injury
Describe the process of platelet aggregation, including the release reaction (ADP), thromboxane synthesis, ADP and thromboxane receptors, glycoprotein IIb/IIIa, and fibrinogen.
- New platelets sick to activates plateless => new ones are activated through release of thromboxane A2 and ADP
- That process puts GP2b/3a in high affinity state
- GP2b/3a are on each platelet
- GP2b/3a binds fibrongen => bridge to lace platelets together
- GP1 is bound to vWF
- Thrombin converts fibrinogen to fibrin
- stable clot formed
What are the 3 mechanisms that can lead to thrombocytopenia?
1) Decreased platelet production
2) Increased platelet destruction
3) Increased consumption/sequestration of platelets in spleen
What are the causes of decreased platelet production as a mechanism that leads to thrombocytopenia
- BM disorders
- BM invasion (cancer, TB)
- Severe nutritional deficiency (B12, folate)
What are the causes of increased platelet destruction as a mechanism that leads to thrombocytopenia
Common cause: ITP
- AutoAbs made directed at platelets => removal by macros
- These AutoAbs are produced in spleen, macros are from spleen
Acute: children, nosebleeds, viral infection => resolves in 2-6 wks
Chronic: adults w/autoimmune disorders, requires tx
What are the causes of consumption/sequestration of platelets as a mechanism that leads to thrombocytopenia
Thrombotic thrombocytopenia purpura (TTP)
- Endo damage => abnormal release of vWF => increased consumption of platelets
- vWF is large b/c ADAMTS13 (normally breaks large vWF to small ones) is absent
What are 3 methods of treating ITP?
What is the mechanism by which corticosteroids increases the platelet count?
- Stunt proliferation of the B cell clone that makes autoAb
- Effect in 7-10 days of tx
What is the mechanism by which IVIG increases the platelet count?
- blocks splenic Fc receptors => prevents binding to autoAb coated platelets
Remember pathoma example: like you're throwing a stick at a dog to distract them from something else
What is the mechanism by which splenectomy increases the platelet count?
- Stops formation of autoAb (spleen did this before)
- Stops production of macros that eat the platelets (spleen did this)
Describe the molecular defect of von Willebrand Disease
- Acquired: Abs develop against vWF
- Congenital: inadequate amount or mutations in vWF gene that cause abnormal protein function
- abnormal platelet/endo interaction => 1ary bleeding disorder, mucosal/skin bleeding
- decrease in Factor 8
Describe the typical clinical course for a patient with von Willebrand Disease
- Bleeding time
- PFA-100 (prolonged w/vWD)
- Factor 8 level
- vW Ag test
- Ristocetin cofactor activity (measures vWF activity)
Describe the general approach to treatment for a patient with von Willebrand Disease
- Synthetic (arginine) vasopressin
Factor 8 replacement
Must avoid aspirin/other platelet inhibiting agents
What are the important questions to ask when obtaining a bleeding history in a pt w/ excessive bleeding?
1) Abnormal bruising?
2) Prolonged bleed after laceration/surgery?
3) Prolonged menstrual bleeding?
4) H/o unusual hematoma, unexplained arthritis
5) Family history
What are the important lab studies to obtain when evaluating a pt w/ excessive bleeding?
- Platelet count -- blood smear
- Bleeding time, PFA
- Thrombin clotting time
- Fibrinogen level
What do an abnormal platelet count and blood smear indicate?
Other hematologic abnormalities
What does bleeding time evaluate?
What does PFA-100 (platelet function analyzer) evaluate?
What does aPTT screen for?
- Abnormal intrinsic pathway
What does PT/INR screen for?
- Abnormal extrinsic pathway
Factor 7 deficiency