Bleeding disorders

Question 1

What are the bleeding disorders caused by vessel wall abnormalites? (6 total)

Answer 1

1) Infections (Meningococcemia)
2) Drug reactions
3) Scurvy and Ehlers-Danlos syndrome (defect in collagen)
4) Henoch-Schonlein purpura
5) Hereditary hemorrhagic telangiectasia (greatest risk for serious bleeding in GI)
6) Perivascular amyloidosis

Question 2

What are the causes of thrombocytopenia?

Answer 2

1) Decreased production (aplastic anemia or leukemia)
2) Decreased survival rate (immunologic, DIC, microangiopathies, or mechanical injury)
3) Sequestration
4) Dilution

Question 3

What disease is caused by IgG autoantibodies selective for platelet membrane glycoproteins IIb-IIIa or Ib-IX that results in thrombocytopenia?

Answer 3

Chronic Immune Throbocytopenic purpura (ITP)

Question 4

What is the difference between chronic and acute immune thrombocytopneic purpura?

Answer 4

1) Acute- childhood disease, self-limited, follows viral illness
2) Chronic - common in women <40, relieved by splenectomy, diagnosis of exclusion

Question 5

What drugs causes Drug induced thrombocytopneia and how do they induce this?

Answer 5

1) Quinine, Quinidine, and vancomycin

2) These drugs bind to platelet glycoprotiens and cause antigenic determinants that are recognized by antibodies

Question 6

Why are megakaryocytes infected with HIV?

Answer 6

Megakaryocytes carry both CD4 and CXCR4; receptors for HIV

Question 7

What are the differences between typical and atypical hemolytic uremic syndrome

Answer 7

1) Typical - due to infection of enterohemorrhagic E. coli
2) Atypical - due to a defect in Factor H, CD46, or Factor I (all prevent an excessive alternative complement pathway response)

Question 8

What is the cause of thrombotic thrombocytopenic purpura?

Answer 8

1) Autoantibodies for ADAMTS13 (acquired)

2) Defect of ADAMTS13 (inherited)

Question 9

What is the cause for hemolytic uremic syndrome?

Answer 9

1) Endothelial dysfunction that promotes platelet aggregation

Question 10

What are the different specific defects of inherited defective platelet function?

Answer 10

1) Impaired adhesion (Bernard-soulier syndrome = defect in Gp1b)
2) Impaired aggregation (Glanzmann thrombasthemia = defective IIb-IIIa glycoprotien)
3) Impaired platelet secretion

Question 11

What syndrome of platelet function impairment is associated impaired platelet adhesion?

Answer 11

Bernard-soulier syndrome- defect in Decreased Gp1b (platelet to vWF adhesion)

Question 12

What syndrome of platelet function impairment is associated with impaired platelet aggregation?

Answer 12

Glanzmann thrombasthemia- defect in IIb-IIIa glycoprotein

Question 13

Where is vWF produced? Where else is it found?

Answer 13

1) Endothelial cells and Kupffer cells

2) Alpha granules of platelets

Question 14

What are the different types of Von Willebrand Factor Disease?

Answer 14

1) Type 1 - autosomal dominant; quantitative defect
2) Type 2 - qualitative defect (2A- autosomal dominant)
3) Type 3 - autosomal recessive; qualitative defect

Question 15

What are the general features of vWF Disease?

Answer 15

1) Mild bleeding
2) Spontaneous bleeding from mucous membranes (epitaxis)
3) Normal platelet count

Question 16

What are the general causes of bleeding disorders?

Answer 16

1) Vessel wall Abnormalities
2) Thrombocytopenia
3) Defective platelet function
4) Defective abnormalities in clotting factors

Question 17

Why is there a prolonged PTT in vWF disease type 1 and 3?

Answer 17

1) Because vWF is closely associated with VIII by stabilizing it. If vWF is decreased or dysfunctional it causes a decrease in VIII (intrinsic coagulation factor)

Question 18

What is the cause of Hemophilia A?

Answer 18

1) A X-linked recessive defect in coagulation factor VIII
2) Defect causes coagulation problem as well as inappropriate fibrinolysis due to decreased activation of thrombin activated fibrinolysis inhibitor (TAFI)

Question 19

Clinical Features of Hemophilia A and B

Answer 19

1) Increased PTT
2) Severe bleeding with trauma
3) Spontaneous hemorrhaging of the joints
4) Petechiae are absent
5) Both are X linked recessive

Question 20

What are the causes of DIC?

Answer 20

1) Release of tissue factor
( heat stroke, massive burns, massive trauma, obsteric complciations)
2) Wide spread injury to endothelial cells
(Sepsis, SLE, Neoplasms, hypoxia, and acidosis)

Question 21

What cancers are most associated with DIC?

Answer 21

1) Acute promyleocytic leukemia and adenocarcinomas

Question 22

What is the treatment for Hemophilia A and B?

Answer 22

1) A = recombinant VIII

2) B = recombinant IX

Question 23

What is the treatment for DIC?

Answer 23

Treat the cause of DIC

Question 24

What are the two results of DIC?

Answer 24

1) Wide spread thrombosis (commonly within the microvasculature)
2) Hemorrhagic diathesis

Question 25

What does wide spread deposition of fibrin found in DIC result in?

Answer 25

1) Microangiopathic hemolytic anemia

Question 26

What are the clinical features of Disseminated intravascular coagulation?

Answer 26

1) Schistocytes
2) Prolonged PT and PTT
3) Positive D dimer
4) Elevated fibrin degradation

Question 27

X linked disease that causes immunodeficiency and thrombocytopenia with eczema

Answer 27

Wiskott-Aldrich Syndrome

Question 28

What is the presentation of vWF disease?

Answer 28

1) Autosomal dominant or recessive (both sexes)
2) Petechiae
3) Prolonged PTT (due to vWF stabilizing VIII)
4) Abnormal platelet function

Question 29

Pt presents with macrohemorrhage (hemarthroses, easy bruising, and increased PTT

Answer 29

Hemophilia A or B

Question 30

Pt. presents with microhemorrhage (mucous membrane bleeding, epitaxis, petechia, purpura) increased bleeding time

Answer 30

Platelet disorder

Question 31

Production of mutant factor V that is resistant to degradation b activated protein C

Answer 31

Factor V Leiden

Question 32

Decreased ability to inactivate factors V and VIII

Answer 32

Protein C or S deficiency