Bleeding Disorders 2 Flashcards
2 causes of thrombocytopenia in patients with HIV
- Megakaryocytes have CD4 and CXCR4 → apoptosis
- B-cell hyperplasia → auto-ab to platelets
Bernard soulier disease is a deficiency of ______ which is required for platelet ______.
- complex 1b-IX (vWF receptor)
- adhesion
Glanzmann thrombasthenia is a deficiency of _____, which is required for platelet _____ .
- glycoprotein 2b-3a (integrin)
- aggregation
______ deficiency → defective platelet release.
Thromboxane
How does aspirin and NSAIDs inhibit platelet aggregation?
- inhibition of COX 1 & COX 2
- no Thromboxane A2 & prostaglandin
How does uremia cause a platelet function defect?
Area codes platelets → preventing aggregation
(ex: diabetic patients who skip dialysis)
What are 3 major signs of coagulopathy
- Large post-traumatic hematomas
- Hemarthrosis
- Prolonged bleeding after laceration
(nose bleeds, menorrhagia, petechiae & purpura, GI bleeding, hematuria)
What diseases are caused by abnormalities of clotting factors?
- Von Willebrand’s disease
- Haemophilia A
- Haemophilia B
- Haemophilia C (rare)
What is the most common hereditary bleeding disorder?
Von Willebrand disease (1-2% of population)
(no gender preference)
Symptoms of Von Willebrand’s disease (3)
- Epistaxis
- Easy bruising
- Bleeding, menorrhagia
(similar to platelet function defect)
Phone Willebrand factor is synthesized by _____ (2).
- Endothelial cells: secreted into plasma & subendothelium
- Megakaryocytes: present in platelet alpha granules
What is the importance of Von Willebrand factor in clot formation?
- Mediates platelet adhesion to endothelium → formation of platelet plug
- Carrier protein for factor VIII
Von Willebrand factor binds _____ on the platelet surface and _____ at the sight of injury, forming a bridge between the platelet and the endothelium to begin a platelet plug.
- GPIb glycoprotein
- exposed endothelium
3 Types of Von Willebrand disease
- Type 1: quantitative
- Type 2: qualitative defect
- Type 3: most severe
(type 1 & 2 are more common)
Haemophilia A & B affects _____ (population)
men only - X-linked
(females are carriers that pass it onto their children; they can be affected but must be homozygous)
Hemophilia A is it a ____ deficiency
factor VIII
(severity depends on how much activity; less activity = more severe)
Why is treatment of hemophilia A difficult?
Repeated doses of factor VIII may development of antibody to the factor. If this is the case, you can bypass this Factor by giving Factor VIIa.
Why is haemophilia B indistinguishable from haemophilia A?
- Haemophilia B = factor IX defect
- Haemophilia A = Factor VIII defect
- They work together to activate Factor X
Why is PT normal in haemophilia A & B?
Because the problem in haemophilia is within the intrinsic system, not the extrinsic system which involves Factor VII
Hemophilia C is a _____defect
Factor XI
(tx: give factor XI or plasma)
While hemophilia A & B are X-linked and mostly affect men, hemophilia C affects ______.
Ashkenazi Jews
(no X-association)
Factor XIII deficiency is similar to ____ deficiency
XI
(rare)
Hemophilia is diagnosed based on _____ (2).
- factor level
- history
DIC is a ______ disorder.
thrombohemorrhagic
(secondary event)
How does DIC occur?
- coagulation activation → formation of thrombi → hypoxia → infarction
- widespread deposition of fibrin contributes to infarction
DIC triggers?
- CA
- Gram- infections
- Trauma/burns
- OB: dead retained retus
- Shock
As DIC progressives platelet and coagulation factors will be used up and this will cause _______.
Bleeding deep inside the body
Vitamin K deficiency →
decreases coagulation factors => PT & PTT will be high
(eat your leafy greens!)
Liver problems will lead to a high _____.
PT
(vitamin K will have high PT & PTT)
