Pathology of Bleeding Disorders

Question 1

What is the most severe type of heparin-induced thrombocytopenia?

Answer 1

Type 2 - increased risk of thrombosis and death

Question 2

True/False. Thrombosis is a “two-hit” disorder.

Answer 2

True - in most patients, the presence of more than one risk factor is needed to manifest thrombosis

Question 3

What is the cause of atypical HUS?

Answer 3

Dysregulation of the complement system causing kidney and other organ damage

Question 4

Haemophilia A is an X-linked recessive disorder that causes deficiency of what coagulation factor?

Answer 4

Factor VIII

Question 5

What is the treatment for Von Willibrand Disease?

Answer 5

Desmopressin, vWF concentrate

Question 6

What is the pathophysiology of Trousseau Syndrome?

Answer 6

Malignant cells produce tissue factor, which activates the coagulation cascade. Other platelet-activating factors and cytokines are produced and neutrophils activated

Question 7

Platelets are formed from the breakdown of what cell?

Answer 7

Megakaryocyte

Question 8

Where is bleeding most likely to occur in cases of hereditary deficiencies in coagulation factors?

Answer 8

Bleeding into joints

Question 9

What is the most common cause of disseminated intravascular coagulation (DIC)?

Answer 9

Sepsis

Question 10

What is the immediate treatment for thrombotic thrombocytopenic purpura?

Answer 10

Plasma exchange - treatment is immediately started if TTP is suspected and altered if another diagnosis is made (ex: HUS)

Question 11

Haemophilia B is an X-linked recessive disorder that causes deficiency of what coagulation factor?

Answer 11

Factor IX

Question 12

What is the normal platelet range for adults?

Answer 12

150,000 - 450,000/uL

Question 13

What is the clinical presentation of HUS?

Answer 13

Hemolytic anemia, thrombocytopenia, acute renal failure

Question 14

What is the cause of immune thrombocytopenic purpura?

Answer 14

IgG autoantibodies against platlets

Question 15

What is the pathophysiology of disseminated intravascular coagulation (DIC)?

Answer 15

Systemic activation of the coagulation cascade that quickly exhausts coagulation. This leads to risk of severe hemorrhage and organ failure.

Question 16

When must a diagnosis of thrombotic microangiopathy be considered?

Answer 16

In patients with a history of anemia, thrombocytopenia, and organ damage

Question 17

Immune thrombocytopenic purpura may remit spontaneously or be treated with corticosteroids, NSAIDs, or anti-D immune globulin. What is the MOA of anti-D immune globulin and potential complication?

Answer 17

Anti-D immune globulin coats RBCs with IgG antibodies to serve as a decoy to splenic macrophages and protect platelets. Hemolytic anemia may occur

Question 18

A predisposition to form blood clots is called…?

Answer 18

Thrombophilia

Question 19

Most cases of HUS are caused by infection with this pathogen.

Answer 19

Shiga-Toxin E. Coli

Question 20

What are the two clinic etiologies of thrombotic microangiopathy?

Answer 20

Thrombotic thrombocytopenia purpura, Hemolytic uremic syndrome

Question 21

This disorder is characterized by thrombosis associated with cancerous causes.

Answer 21

Trousseau Syndrome

Question 22

What class of antibodies is most often involved in idiopathic thrombotic thrombocytopenic purpura?

Answer 22

IgG antibodies targeting ADAMTs13 cysteine-rich domains

Question 23

What is the gold standard test for diagnosing heparin-induced thrombocytopenia?

Answer 23

Serotonin release assay - when activated platelets release serotonin

Question 24

What is the pathophysiology of thrombotic thrombocytopenic purpura?

Answer 24

Targeting of ADAMTS13 enzyme by IgG antibodies prevents breakdown of vWF, thus increasing the risk of clot formation in vessels

Question 25

What vessels are affected by anti-phospholipid syndrome?

Answer 25

Any vessel (arterial/venous) can be affected by thrombosis

Question 26

What is the treatment for antiphospholipid syndrome?

Answer 26

Anticoagulants - dose and duration dependent upon clinical circumstance

Question 27

In children, this thrombocytopenia syndrome is associated with recent viral illness.

Answer 27

Immune thrombocytopenic purpura

Question 28

What is the common clinical presentation of thrombotic thrombocytopenic purpura?

Answer 28

Thrombocytopenia, microangiopathy hemolytic anemia (MAHA), neurologic symptoms, ischemia, renal problems

Question 29

What is the most common bleeding disorder and its inheritance pattern?

Answer 29

Von Willibrand Disease - autosomal dominant

Question 30

Haemophilia C is an autosomal recessive disorder that causes deficiency of what coagulation factor?

Answer 30

Factor XI

Question 31

How do the types of Von Willibrand Disease differ?

Answer 31

Type 1 - most common, mild loss of vWF

Type 2 - qualitative disorder, normal vWF but defective

Type 3 - no vWF, severe

Question 32

Increased numbers of IPFs are found in the blood in patients with immune thrombocytopenic purpura. What are IPFs and the reason for their increase?

Answer 32

IPFs are immature platelets released into the blood before the megakaryocyte can fully break up due to destruction of mature platelets

Question 33

What is the pathophysiology of heparin-inducted thrombocytopenia?

Answer 33

IgG antibodies against the heparain-PF4 complex that leads to platelet activation. Activated platelets activate other platelets, increasing the risk of thrombosis. Platelets marked with IgG are prematurely destroyed.

Question 34

What type of cancer is associated with the highest risk of Trousseau Syndrome?

Answer 34

Pancreatic Cancer

Question 35

What is thrombocytopenia?

Answer 35

Decrease in platelet numbers - may be due to decreased production or increased destruction (immune or non-immune)

Question 36

Cases of hereditary thrombotic thrombocytopenic purpura are least common. What gene is mutated in these cases?

Answer 36

ADAMTS13

Question 37

What protein receptor enables binding between platlets?

Answer 37

GpIIb/IIIa