Coagulation Disorders: Hemorrhagic

Question 1

Define Hemostasis

Answer 1

process of blood clot formation at site of vessel injury

Question 2

Explain the process of coagulation, using terms primary and secondary hemostasis

Answer 2

primary hemostasis: (results in platelet plug formation)
1. Vasoconstriction
2. platelet adhesion to collagen (VWF recruits)
3. platelet activation: platelets release ADP and thromboxane A2 recruiting more platelets to aggregate. thromboxane A2 and release of serotonin causes further vasoconstriction
4. platelet aggregation (platelet plug formation)

Secondary hemostasis: (coagulation cascade)

Intrinsic pathway (F 8, 9, 11 , 12)
1. F12 activated into F 12a -> which then activates F11 into F11a which then activates F9 into F9a which then forms a complex with F8 (needs platelet factor 3 and calcium)
2. complex of F9a and F8 activates the common pathway

Extrinsic pathway (F 7, 9)
1. damaged tissue releases tissue factor 3 (tf3) which activates F7. F7a promotes the activation of F9 in the intrinsic pathway, and can also directly activate F10 of the common pathway

Common pathway: (F 2, 5, 10, 13)
1. F10 activated by either F9a F8 complex, or F7a into F10a. F10a with FV activates the prothrombin activator which activates F2 (prothrombin) to F2a (thrombin)
2. F2a (thrombin) then activates fibrinogen to fibrin (polymerized) , F13 activated by F2a then crosslinks the fibrin polymers, forming a fibrin mesh over the platelet plug.

Question 3

Identify the signs and symptoms of abnormal bleeding

Answer 3

Skin and mucosal bleeding (issue with primary hemostasis)
- easy bruising
- nose bleeds
- heavy menstrual period
- GI bleeding

Deep tissue bleeding (issue with secondary hemostasis)
- muscle and joint bleeds
- sometimes mucosal bleeding
- bleeding severity is associated with factor level

Question 4

How can we utilize an approach of history, physical exam, and common lab tests to diagnose bleeding disorders?

Answer 4

History -> hereditary disorders/ pattern of inheritance
medical history -> what medications? acquired cases of abnormal bleeding are much more common
physical exam -> type of bleeding; is the bleeding skin and mucosal membrane or deep tissue?

Question 5

What is the role of VWF in primary and secondary hemostasis

Answer 5

Primary hemostasis:
- help platelets adhere to blood vessel wall
- promotes platelet aggregation

Secondary hemostasis:
- acts as a carrier protein for factor VIII

Question 6

Bleeding/bruising tendency can be separated into 3 causes, list these causes and an inherited/ acquired condition for each

Answer 6

Blood vessel problem
- inherited: hereditary hemorrhagic telangiectasia (small vessel malformations around nose/lips/tongue)
- acquired: Vitamin C deficiency (reduced collagen production -> blood vessel fragility )

Platelet or VWF problem
- inherited: Von Willebrand’s disease (mucosal bleeding and heavy menstrual bleeds) 3 types include quantitative partial deficiency, functional abnormality and complete deficiency
- acquired: aspirin

Clotting factor problem
- inherited: hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) (platelet plug forms, but slow generation of thrombin , also weak and fragile)
- acquired: Drugs (heparin, DOAC, VKA), Liver disease

Question 7

What are the 3 basic lab tests for bleeding disorders? what do these test? What are some expected results?

Answer 7

Complete blood count (platelet count/morphology): detects thrombocytopenia and abnormal platelet morphology
Partial thromboplastin time (PTT) (test of intrinsic and common pathway): detect low F8,F9,F11,F12 as well as overlapping with INR test, low F10, F5, F2, fibrinogen)
Prothrombin time and INR (PT) (test of extrinsic and common pathway): detect low F7 (PT and INR), low in F10, F5, F2, fibrinogen (INR)

Question 8

Explain liver disease as an acquired clotting factor problem

Answer 8

liver disease results in decreased clotting factor production
- can be caused by cirrhosis, hepatitis, etc…
- impaired synthesis of factors 2 7 9 10 by liver cells
- decreased production of factor 5 and fibrinogen in severe liver disease
- functional abnormality of fibrinogen
- thrombocytopenia
- however, anticoagulants are also reduced, so the net result may be prothrombotic -> complex issue