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)
What are 4 bleeding disorder true emergencies?
- Hemophilia A or B w/bleeding
- ITP w/bleeding
- TTP
- DIC
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
Which CA are most likely to cause DIC?
mucin-secreting: adenocarcinoma of pancreas or prostate or acute promyelocytic leukemia
(tumor cells express and expose or release tissue factor)
DIC patients will already have ______
thrombocytopenia
(and platelets below 50,000 (50%))
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)
Fragility of the vessel walls will present w/petechiae and purpura but the _____ will be normal.
platelet counts & coagulation tests
What is a must not miss diagnosis for fragility of vessel walls?
Petechiae and purpura due to meningococcemia
(TQ!!!)
What are causes of fragility of vessel walls?
- Infection
- Drug reaction
- Collagen disease
- Perivascular amyloidosis
When would you order laboratory investigation for bleeding disorders?
- Personal or family history
- Laboratory findings suggesting possible bleeding disorder
When do you test for the rarer bleeding disorders (Factor XIII, plasminogen activator inhibitor)?
when severe bleeding problem has no other answers from the previous investigations
