Hemostasis: Approach to Patient (complete) Flashcards Preview

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What are the events occurring during primary hemostasis?

- Adhesion
- Activation
- 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?

- Serotonin
- Calcium


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?

Acid hydrolases


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
- Myelodysplasia
- Leukemia
- BM invasion (cancer, TB)
- Chemo
- 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?

1) Corticosteroids
3) Splenectomy


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

Leads to:
- 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
6) Drugs/meds


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?

Primary hemostasis


What does PFA-100 (platelet function analyzer) evaluate?

Primary hemostasis


What does aPTT screen for?

- Abnormal intrinsic pathway



What does PT/INR screen for?

- Abnormal extrinsic pathway

Factor 7 deficiency


What does thrombin clotting time (TCT) evaluate?

- Fibrinogen defects
- Presence of fibrin split products
- Heparin effects