Bleeding Disorders

Question 1

What is the most common inherited bleeding disorder?

Answer 1

von Willebrand Disease

Question 2

Petechiae, purpura or ecchymoses suggest what type of bleeding disorder?

Answer 2

thrombocytopenia

Question 3

Enlarged spleen, liver or lymph nodes suggest what type of bleeding disorder?

Answer 3

chronic infections or malignancies

Question 4

Telangiectasias suggest what type of bleeding disorder?

Answer 4

Osler-Weber-Rendu

Question 5

Hyperextensible joints or paper-thin scars suggest what type of bleeding disorder?

Answer 5

Ehlers-Danlos

Question 6

Skin plaques or scalloped tongue suggest what type of bleeding disorder?

Answer 6

amyloid

Question 7

Musculoskeletal abnormalities suggest what type of bleeding disorder?

Answer 7

hemophilia

Question 8

What is the mutation seen in vWD?

Answer 8

quantitative or qualitative deficiency of von Willebrand factor

Question 9

What clinical symptoms is characteristic of vWD?

Answer 9

mucocutaneous bleeding

Question 10

What is the function of vWF?

Answer 10

carrier protein for factor VIII
ligand to bind GPIB receptor on platelets for initiation of platelet adhesion to damaged blood vessel

Question 11

Where is vWF made?

Answer 11

endothelial cells & megakaryocytes

Question 12

Where is Factor VIII produced?

Answer 12

liver & kidney

Question 13

What are the 3 main types of vWD?
Which type is most common?

Answer 13

• Type 1 - MC (80%)
  
  • heterozygous or partial quantitative deficiency vWF
  • mild disease
• Type 2
  
  • abnormal vWF produced
  • variable severity
• Type 3
  
  • homozygous
  • absent or severe deficiency vWF
  • plasma levels factor VIII severely decreased
  • clinically looks like hemophilia A

Question 14

How do the different types of vWD in the multimer analysis?

Answer 14

• Type 1: all multimes, but reduced quantity
• Type 2: variable
• Type 3: none

Question 15

What is the cause of Hemophilia A?

What are the different severities?

Answer 15

deficiency of factor VIII

severe <1%

moderate 1-5%

mild >5%

Question 16

Hemophilia A has what type of inheritance pattern?

Answer 16

X-linked recessive

Question 17

What are the clinical symptoms of a patient with Hemophilia A?

Answer 17

bleeding into joints

hemophilic arthropathy

bleeds with minor trauma

NO mucocutaneous bleeding

Question 18

What lab values would you expect to see in a patient with Hemophilia A?

Answer 18

• prolonged PTT
  
  • complete correction with mixing study
• genetic testing - prenatal testing
• normal PT, TT & bleeding time
  
  • extrinsic & common pathway are in tact
  • platelet function & vascular integrity are also in tact

Question 19

What is the treatment for Hemophilia A?

Answer 19

DDAVP mild cases

factor VIII concentration moderate to severe disease

Question 20

What are possible complications to treatment of Hemophilia A?

Answer 20

inhibitors factor VIII

HIV, Hepatitis, Parvovirus B19 (b/c acquired form transfusion)

Question 21

What is the mutation in Hemophilia B?

It has what type of inheritance pattern?

Answer 21

deficiency factor IX

X-linked recessive

Question 22

What is the most common cause of acquired factor deficiency?

Answer 22

Liver disease

Question 23

Vitamin K is required for function of what factors?

Answer 23

factors

II, VII, IX, X

protein C & protein S

Question 24

Normal hemostasis has what 3 components?

Answer 24

1. vascular wall integrity
2. Platelets (adequate # & function)
3. coagulation cascade

Question 25

What is Virchow's Triad?

Answer 25

alone or in combo predisposes to thrombosis * Endothelial injury * Hypercoaguability * Abnormal blood flow

Question 26

What situations would warrant a complete thrombophilia workup?

Answer 26

thromboembolic event under age 50 unprovoked event at any age

Question 27

What mutation causes Factor V Leiden?

Answer 27

point mutation factor V that makes it resistant to proteolytic action of activated protein C protein C normally degrades activated factor V & factor VIII

Question 28

What is the most common hereditary predisposition to venous thrombosis?

Answer 28

Factor V Leiden

Question 29

Individuals homozygous for Factor V Leiden have what relative risk of developing venous thrombosis?

Answer 29

80x

Question 30

Prothrombin gene mutation is associated with what molecular abnormality?

Answer 30

elevated levels of prothrombin & subsequent increased risk of thrombosis increased levels TAFI- protein that inhibits clot lysis, so clots last longer

Question 31

Factor VIII levels what percent of normal are associated with increased risk of venous & arterial thrombosis? This is often seen in what situation?

Answer 31

150% inflammatory states (acute phase reactant)

Question 32

What are the 3 common risk factors for venous thromboembolism?

Answer 32

factor V Leiden prothrombin gene mutation elevated factor VIII

Question 33

What test do you perform if you suspect Factor V Leiden?

Answer 33

screen: activated protein C resistance genetic testing is definitive

Question 34

Deficiency in Protein C increases risk of DVT in what specific locations?

Answer 34

legs & mesenteric veins pulmonary embolism

Question 35

Protein C & Protein S deficiency are associated with what warfarin-related issue?

Answer 35

warfarin-induced skin necrosis

Question 36

What is the clinical presentation of neonates with severely decreased levels of protein C?

Answer 36

DIC purpura fulminans neonatorum

Question 37

What are acquired increases in protein C that may mask deficiencies?

Answer 37

ischemic heart disease pregnancy post-menopausal state hormone replacement therapy oral contraceptives

Question 38

Patients with deficiencies in protein C, protein S & antithrombin often have a thromboembolic even before what age?

Answer 38

45

Question 39

How long after a thrombotic event should you wait before thrombophilia testing?

Answer 39

2 weeks

Question 40

What thrombophilia tests are not affected by anticoagulants or active thrombosis?

Answer 40

* activated protein C resistance (APCR) * homocysteine * anticardiolipin antibodies * genetic tests for V leiden and prothrombin gene

Question 41

What factors predispose to **venous** thrombosis?

Answer 41

* factor V Leiden * prothrombin mutation * elevated VIII levels * increased levels II, IX, XI * deficiencies protein C, S

Question 42

What factors predispose to **arterial** thrombosis?

Answer 42

* heparin platelet antibodies * hyperhomocysteinemia * antiphospholipid antibodies * elevated levels factor I, V, VII, vWF * deficiency antithrombin