Coagulation disorders: Hemorrhagic Flashcards
What is hemostasis?
Process of blood cloot formation at the site of vessel injury
Explain the process of coagulation, using the terms primary and secondary hemostasis.
Primary hemostasis is when your body forms a temporary plug to seal an injury. To accomplish that, platelets that circulate in your blood stick to the damage tissue and activate. Furthermore, vasoconstriction limits blood flow and the activated platelets form a stick plug to stop blood loss from the damaged area.
- Injury to vessel lining triggers release of clotting factors, and these clotting factors convert prothrombin to thrombin
Secondary hemostasis is when the body stabilzies the platelet plug. Thrombin converts fibrinogen (soluble) to fibrin (insoluble). Fibrin strands adhere to the platelet plug and form an insoluble clot.
What is the role of vWF in primary and secondary hemostasis?
Primary:
- Helps platelet adhere to the blood vessel wall by bridging collagen with platelet through GPIb-IX receptor
- Promotes platelet aggregation
Secondary
- Acts as a carrier protein for factor VIII
What are the causes of abnormal bleeding and what are their signs and symptoms?
- Decreased clotting or bleeding disorders
- BV damages
- Reduced platelets
- Platelet dysfunction
- Reduced coagulation factors/dysfunction - Increased clotting of hypercoagulability
- BV obstruction
- High platelets
- Increased coagulation factors
- High Hb
- Reduced natural anticoagulant (AT, PC, PS)
What is the clinical presentation of bleeding disorders?
Skin & Mucosal Bleeding (Mucocutaneous)
- Caused by problems with primary hemostasis
1. Easy brusing
2. Epistaxis (nosebleed)
3. Menorrhagia
4. GI bleeding
Deep tissue bleeding
- Caused by problems with secondary hemostasis
1. Mainly muscle and joint bleeds
2. Sometimes mucosal bleeding
3. Bleeding severity is associated with factor level
What are the bleeding disorders caused by blood vessel problems? What are their clinical symptoms and manifestations?
- Hereditary Hemorrhagic Telangiectasia (inherited)
- Autosomal dominant
- LOCALIZED ANGIODYSPLASIA
- Characteristic appearance of TELANGIECTASIAS around nose, lips and tongue - Vitamin C deficiency (acquired)
- Increased BV fragility
- Petechiae, perifollicular hemorrhage, purpura/bruising
What is the most common hereditary bleeding disorder? What are the clinical symptoms associated with this disease.
Von Willebrand Disease
- Autosomal dominant/recessive hence both females and males are affected
Clinical symptoms of VWD
- Mucosal bleeding
- Menorrhagia
- Preoperative hemorrhage occurs in patients with significant decrease in vWF
What is the platelet associated function and Factor VIII binding capacity for Type 2B and 2N VWD?
2B
Platelet associated function: increased affinity for GPIb
Factor VIII binding capacity: normal
2N
Platelet-associated fcn: normal
Factor VIII binding capacity: reduced
What are the causes of congenital platelet disorders? (3) Give one example of a congenital platelet disorder.
Causes:
- Enzyme deficiency
- Abnormal granules
- Metabolism abnormality
Example: Gray Platelet Syndrome
- Macrothrombocytopenia with deficient a-granules
What are the causes of acquired platelet dysfunction?
Medications
Herbal supplements
Kidney failure
Myeloproliferative neoplasm
What is Hemophilia A caused by?
X-linked inherited deficiency of Factor VIII
- Due to decreased amount
- Functionally abnormal protein
- Or both
What is Hemophilia B caused by? What are the clinical symptoms of hemophilia B?
Factor IX deficiency
- Decreased clotting factor production
- Dysfunctional circulating clotting factor
Clinical symptoms
- Weak, fragile clot because of slow generation of thrombin
- Prolonged/delayed bleeding after injury
What are the clinical manifestations of liver disease?
- Causes of liver disease like alcoholic cirrhosis can impair the synthesis of FII, VII, IX, X by liver parenchymal cells.
- In severe liver disease, production of FV and fibrinogen is decreased.
3.Dysfibrinogenemia -> functional abnormality of fibrinogen
What are the basic laboratory testing for bleeding disorders?
- Complete blood count
- Detects thrombocytopenia
- Abnormal platelet morphology - PTT - Test of INTRINSIC & Common Pathway
- Low F8, F9, F11, F12 level (PTT only)
- If low in F1, F2, F5, F10 (Both INR & PTT abnormal) - PT & INR - Test of EXTRINSIC & Common Pathway
- Low F7 (PT & INR) - Factor Assays
What are the caused of elevated APTT? PT/INR?
Elevated APTT:
1. Intrinsic clotting factor(s) deficiency
2. Factor inhibitor
3. Medication
PT and INR
1. Factor VII deficiency
2. Vitamin K deficiency or antagonist
3. Liver disease
