Bleeding Disorders 2

Question 1

2 causes of thrombocytopenia in patients with HIV

Answer 1

1. Megakaryocytes have CD4 and CXCR4 → apoptosis
2. B-cell hyperplasia → auto-ab to platelets

Question 2

Bernard soulier disease is a deficiency of ______ which is required for platelet ______.

Answer 2

• complex 1b-IX (vWF receptor)
• adhesion

Question 3

Glanzmann thrombasthenia is a deficiency of _____, which is required for platelet _____ .

Answer 3

• glycoprotein 2b-3a (integrin)
• aggregation

Question 4

______ deficiency → defective platelet release.

Answer 4

Thromboxane

Question 5

How does aspirin and NSAIDs inhibit platelet aggregation?

Answer 5

1. inhibition of COX 1 & COX 2
2. no Thromboxane A2 & prostaglandin

Question 6

How does uremia cause a platelet function defect?

Answer 6

Area codes platelets → preventing aggregation

(ex: diabetic patients who skip dialysis)

Question 7

What are 3 major signs of coagulopathy

Answer 7

1. Large post-traumatic hematomas
2. Hemarthrosis
3. Prolonged bleeding after laceration

(nose bleeds, menorrhagia, petechiae & purpura, GI bleeding, hematuria)

Question 8

What diseases are caused by abnormalities of clotting factors?

Answer 8

1. Von Willebrand’s disease
2. Haemophilia A
3. Haemophilia B
4. Haemophilia C (rare)

Question 9

What is the most common hereditary bleeding disorder?

Answer 9

Von Willebrand disease (1-2% of population)

(no gender preference)

Question 10

Symptoms of Von Willebrand’s disease (3)

Answer 10

1. Epistaxis
2. Easy bruising
3. Bleeding, menorrhagia

(similar to platelet function defect)

Question 11

Phone Willebrand factor is synthesized by _____ (2).

Answer 11

1. Endothelial cells: secreted into plasma & subendothelium
2. Megakaryocytes: present in platelet alpha granules

Question 12

What is the importance of Von Willebrand factor in clot formation?

Answer 12

1. Mediates platelet adhesion to endothelium → formation of platelet plug
2. Carrier protein for factor VIII

Question 13

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.

Answer 13

• GPIb glycoprotein
• exposed endothelium

Question 14

3 Types of Von Willebrand disease

Answer 14

1. Type 1: quantitative
2. Type 2: qualitative defect
3. Type 3: most severe

(type 1 & 2 are more common)

Question 15

Haemophilia A & B affects _____ (population)

Answer 15

men only - X-linked

(females are carriers that pass it onto their children; they can be affected but must be homozygous)

Question 16

Hemophilia A is it a ____ deficiency

Answer 16

factor VIII

(severity depends on how much activity; less activity = more severe)

Question 17

Why is treatment of hemophilia A difficult?

Answer 17

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.

Question 18

Why is haemophilia B indistinguishable from haemophilia A?

Answer 18

• Haemophilia B = factor IX defect
• Haemophilia A = Factor VIII defect
• They work together to activate Factor X

Question 19

Why is PT normal in haemophilia A & B?

Answer 19

Because the problem in haemophilia is within the intrinsic system, not the extrinsic system which involves Factor VII

Question 20

Hemophilia C is a _____defect

Answer 20

Factor XI

(tx: give factor XI or plasma)

Question 21

While hemophilia A & B are X-linked and mostly affect men, hemophilia C affects ______.

Answer 21

Ashkenazi Jews

(no X-association)

Question 22

Factor XIII deficiency is similar to ____ deficiency

Answer 22

XI

(rare)

Question 23

What are 4 bleeding disorder true emergencies?

Answer 23

1. Hemophilia A or B w/bleeding
2. ITP w/bleeding
3. TTP
4. DIC

Question 24

Hemophilia is diagnosed based on _____ (2).

Answer 24

1. factor level
2. history

Question 25

DIC is a ______ disorder.

Answer 25

thrombohemorrhagic | (secondary event)

Question 26

How does DIC occur?

Answer 26

* coagulation activation → formation of thrombi → hypoxia → infarction * widespread deposition of fibrin contributes to infarction

Question 27

DIC triggers?

Answer 27

1. CA 2. Gram- infections 3. Trauma/burns 4. OB: dead retained retus 5. Shock

Question 28

Which CA are most likely to cause DIC?

Answer 28

mucin-secreting: adenocarcinoma of pancreas or prostate or acute promyelocytic leukemia (tumor cells express and expose or release tissue factor)

Question 29

DIC patients will already have \_\_\_\_\_\_

Answer 29

thrombocytopenia (and platelets below 50,000 (50%))

Question 30

As DIC progressives platelet and coagulation factors will be used up and this will cause \_\_\_\_\_\_\_.

Answer 30

Bleeding deep inside the body

Question 31

Vitamin K deficiency →

Answer 31

decreases coagulation factors =\> PT & PTT will be high (eat your leafy greens!)

Question 32

Liver problems will lead to a high \_\_\_\_\_.

Answer 32

PT (vitamin K will have high PT & PTT)

Question 33

Fragility of the vessel walls will present w/petechiae and purpura but the _____ will be normal.

Answer 33

platelet counts & coagulation tests

Question 34

What is a must not miss diagnosis for fragility of vessel walls?

Answer 34

Petechiae and purpura due to meningococcemia ***_(TQ!!!)_***

Question 35

What are causes of fragility of vessel walls?

Answer 35

1. Infection 2. Drug reaction 3. Collagen disease 4. Perivascular amyloidosis

Question 36

When would you order laboratory investigation for bleeding disorders?

Answer 36

1. Personal or family history 2. Laboratory findings suggesting possible bleeding disorder

Question 37

When do you test for the rarer bleeding disorders (Factor XIII, plasminogen activator inhibitor)?

Answer 37

when severe bleeding problem has no other answers from the previous investigations