Hemostasis: Approach to Patient (complete) Flashcards Preview

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Flashcards in Hemostasis: Approach to Patient (complete) Deck (29):
1

What are the events occurring during primary hemostasis?

- Adhesion
- Activation
- Aggregation of platelets

forms a platelet plug

2

What are the events occurring during secondary hemostasis?

- Formation of fibrin network (generated by coag cascade)

Stabilizes the platelet plug

3

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

4

What do dense granules contain?

- ATP
- ADP
- Serotonin
- Calcium

5

What do alpha granules contain?

Proteins essential for platelet function:
- procoag proteins (fibrinogen, Factor 5, vWF)
- platelet factors for activation
- growth factors

6

What do lysosomal granules contain?

Acid hydrolases

7

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

8

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

9

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

10

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

11

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

12

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)

13

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

14

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

15

What are 3 methods of treating ITP?

1) Corticosteroids
2) IVIG
3) Splenectomy

16

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

17

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

18

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)

19

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

20

Describe the typical clinical course for a patient with von Willebrand Disease

Tests:
- Bleeding time
- PFA-100 (prolonged w/vWD)
- Factor 8 level
- vW Ag test
- Ristocetin cofactor activity (measures vWF activity)

21

Describe the general approach to treatment for a patient with von Willebrand Disease

DDAVP
- Synthetic (arginine) vasopressin

Factor 8 replacement

Must avoid aspirin/other platelet inhibiting agents

22

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

23

What are the important lab studies to obtain when evaluating a pt w/ excessive bleeding?

- Platelet count -- blood smear
- Bleeding time, PFA
- APTT
- PT/INR
- Thrombin clotting time
- Fibrinogen level

24

What do an abnormal platelet count and blood smear indicate?

Thrombocytopenia!!

Other hematologic abnormalities

25

What does bleeding time evaluate?

Primary hemostasis

26

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

Primary hemostasis

27

What does aPTT screen for?

- Abnormal intrinsic pathway

Hemophilia

28

What does PT/INR screen for?

- Abnormal extrinsic pathway

Factor 7 deficiency

29

What does thrombin clotting time (TCT) evaluate?

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