Module 4

Question 1

Acquired vascular and extravascular disorders

Answer 1

Senile purpura
Simple easy bruising
Secondary vascular purpuras

Question 2

Inherited vascular and extravascular disorders

Answer 2

Hereditary hemorrhagic telangiectasia
Ehlers-Danlos syndrome
Marfan syndrome
Osteogenesis imperfecta
Homocystinuria
Pseudo Xanthoma Elasticum

Question 3

Purpura

Answer 3

A rash associated with leakage of blood into the skin and/or mucous membranes

Question 4

Secondary vascular purpuras

Answer 4

Endothelial damage from a variety of causes, such as immune damage, hypertension, scurvy, increased pressure, liver disease, etc.

Question 5

Hereditary Hemorrhagic Telangiectasia (HHT)

Answer 5

AKA Osler-Weber-Rendu disease
Most common inherited vascular disorder (but still rare)
AV fistula are comon in HHT
HHT is an autosomal dominant defect in the subendothelial colagen that results in:
Dilations of capillaries (telangiectasia)
Loss of vascular patency (producing petechiae)
Spontaneous bleeds from mucous membranes

Question 6

Most common inherited vascular disorder

Answer 6

Hereditary hemorrhagic telangiectasia (HHT or Osler-Weber-Rendu disease)

Question 7

Ehlers-Danlos syndromes

Answer 7

Loss of elasticity in the epidermis and sub-epidermal tissues (people with very deformable skin)

Question 8

Marfan syndrome

Answer 8

Defect in chromosome 15 resulting in abnormal fibrillan in connective tissue and weakness
Aortic prolapse is one serious consequence

Question 9

Pseudo Xanthoma Elasticum

Answer 9

An inherited disorder of elastin in which elastic tissues in the body become mineralized

Question 10

Quantitative disorders of platelets

Answer 10

Decreased platelets (thrombocytopenia) or increased platelets (thrombocytosis) in circulation

Question 11

Increased platelets in circulation

Answer 11

Thrombocytosis

If platelet count exceeds 1000 x 10^9/L, the term thrombocythemia is used

Question 12

The most common single cause of abnormal bleeding

Answer 12

Thrombocytopenia

Question 13

Clinical findings in thrombocytopenia

Answer 13

Skin purpura (bruising and petechiae)
Mucosal hemorrhages
Increased bleeding after trauma

Question 14

Easy fix for a patient with thrombocytosis

Answer 14

Aspirin

Inhibits cyclooxygenase to inhibit platelet aggregation

Question 15

Thrombotic thrombocytopenic purpura (TTP)

Answer 15

Rare condition where there is excessive consumption of platelets (excessive platelet adhesion, aggregation, coagulation)
Deficiency of the enzyme ADAMTS-13, which is required to break up ultra large VWF adhesive multimers. A deficiency of the enzyme results in the presence of adhesive ULVWF multimers in the plasma, and therefore widespread platelet aggregation and thrombi

Question 16

Specific lab findings in TTP

Answer 16

Increased megakaryocytes in the bone marrow
Increased megathrombocytes in the blood smear
Increased platelet aggregation seen in the blood film
Decreased platelet survival (radioisotope method)

Question 17

Immune thrombocytopenic purpura (ITP)

Answer 17

A condition in which there is increased destruction of platelets due to platelet antibodies
A platelet antibody sensitizes the platelets and causes their premature removal by macrophages in the spleen
Can be acute or chronic
Chronic ITP is the 2nd most common cause of thrombocytopenia

Question 18

Most common cause of thrombocytopenia

Answer 18

Decreased/ineffective production of platelets

Can be caused by marrow hypoplasia

Question 19

Conditions that cause splenomegaly can have what effect on platelet count

Answer 19

Decreased platelet count

With an enlarged spleen, there is increased splenic pooling of platelets, therefore less platelets in circulation

Question 20

Causes of marrow hypoplasia

Answer 20

Overcrowding/replacement of normal hematopoietic cells in the marrow (acute leukemia or myelofibrosis)
Inherited (Wiskott-Aldrich syndrome)
Acquired (drugs, chemicals, radiation)

Question 21

Disorders of platelet secretion/release reactions

Answer 21

Storage pool diseases (granule defects) - dense and/or alpha granules
Primary secretion defects - due to deficiencies of enzymes and other secondary messengers that transmit signals from surface receptors to cause the release of the granule contents

Question 22

Thrombasthenia (Glanzmann disease)

Answer 22

Inherited functional defect of platelets
Failure of primary aggregation
Caused by reduced amount of GPIIb/IIIa (fibrinogen cannot be bound to the platelet membrane)

Question 23

Lab findings in thrombasthenia (Glanzmann disease)

Answer 23

Bleeding time greatly prolonged
Clot retraction is defective
Platelet adhesion to collagen is normal
Platelet aggregation - abnormal with ADP, epinephrine, thrombin and serotonin, normal with ristocetin

Question 24

Bernard-Soulier Syndrome (BSS) is also known as

Answer 24

Giant platelet syndrome

Question 25

Bernard-Soulier Syndrome (BSS)

Answer 25

Severe inherited failure of platelet adhesion caused by reduced amounts of GPIb/IX (vWF cannot be bound to the platelet membrane)

Question 26

Bernard-Soulier Syndrome (BSS) clinical symptoms

Answer 26

Severe subcutaneous, mucosal, and visceral bleeding which is often fatal

Question 27

Lab findings in Bernard-Soulier Syndrome (BSS)

Answer 27

Very large megathrombocytes in the blood film Increased numbers of dense granules Bleeding time greatly prolonged Platelet count is normal or decreased Platelet adhesion is normal in vitro Platelet aggregation is normal with ADP and other aggregating agents, abnormal with ristocetin

Question 28

Platelet count = normal, platelet morphology=normal, closure time/bleeding time = prolonged, platelet aggregation with ristocetin = normal, platelet aggregation with ADP = abnormal. What is the syndrome present?

Answer 28

Glanzmann thrombasthenia

Question 29

Platelet count = normal or decreased, platelet morphology=large platelets, closure time/bleeding time = prolonged, platelet aggregation with ristocetin = abnormal, platelet aggregation with ADP = normal. What is the syndrome present?

Answer 29

Bernard-Soulier syndrome

Question 30

Two bleeding disorders in which platelets fail to aggregate with ristocetin

Answer 30

Bernard-Soulier syndrome and von Willebrand disease

Question 31

Deficiencies of which factors produce bleeding proportional to their deficiency?

Answer 31

IX, VIII, X, V, II, and I

Question 32

Severe coagulation factor deficiency

Answer 32

Less than 1% of the normal level in plasma

Question 33

Moderate coagulation factor deficiency

Answer 33

1-5% of the normal level in plasma

Question 34

Mild factor deficiency

Answer 34

5-25% of normal level in plasma

Question 35

Hemophilia A is a deficiency of what?

Answer 35

Factor VIII:C

Question 36

Hemophilia B is a deficiency of what?

Answer 36

Factor IX (also called Christmas disease)

Question 37

Gene affected in hemophilia A

Answer 37

Xq28

Question 38

Gene affected in hemophilia B

Answer 38

Xq27

Question 39

Therapy for hemophilia A

Answer 39

Factor VIII infusion

Question 40

Complications in treatment for hemophilia A

Answer 40

Development of immune VIII antibodies

Question 41

Therapy for hemophilia B

Answer 41

Prothrombin group concentrate or factor IX concentrate

Question 42

Von Willebrand disease is a disorder of what?

Answer 42

Platelet function (adhesion)

Question 43

Chromosome that is defective in Von Willebrand disease

Answer 43

Chromosome 12

Question 44

Treatment in Von Willebrand disease

Answer 44

Infusion of factor VIII concentrate

Question 45

Most common inherited bleeding disorder

Answer 45

Von Willebrand disease

Question 46

Most useful tests for workup of Von Willebrand disease

Answer 46

Platelet agglutination with ristocetin | Platelet aggregation with ristocetin (reduced)

Question 47

PIVKA

Answer 47

Proteins induced by vitamin K absence | Non-carboxylated, inactive abnormal prothrombin factor molecules

Question 48

Lupus anticoagulant

Answer 48

An antibody that binds to phospholipids and proteins associated with the cell membrane Interferes with interactions between cell membrane and clotting factors Often associated with venous thrombosis

Question 49

Anticardiolipin antibody (ACA)

Answer 49

Antibody often directed against cardiolipin, and important component of the inner mitochondrial membrane Often associated with arterial thrombosis

Question 50

Disseminated intravascular coagulation (DIC)

Answer 50

AKA secondary fibrinolysis A condition in which there is widespread intravascular coagulation and secondary fibrinolysis, resulting in the consumption and destruction of coagulation factors to the point of a factor deficiency, thrombocytopenia, and abnormal bleeding

Question 51

Causes of DIC

Answer 51

Any situation that causes exposure of a lot of foreign surfaces to the blood Eg. bacterial endotoxins, liver disease, major surgery/crash injuries

Question 52

To diagnose DIC, lab findings should confirm:

Answer 52

``` Test results should confirm all of: Activation of coagulation Activation of fibrinolysis Inhibitor consumption End organ damage or failure ```

Question 53

Lab results in DIC

Answer 53

Factor deficiencies (prolonged PT and/or PTT) Thrombocytopenia Increased FDP and fdp Schistocytes

Question 54

Primary fibrinolysis

Answer 54

Activation of fibrinolysis in the absence of coagulation | Abnormal activation of plasminogen to plasmin which destroys fibrinogen (not fibrin, as there is no fibrin clot)

Question 55

Differences in lab findings in primary fibrinolysis and secondary fibrinolysis

Answer 55

In primary fibrinolysis, D-dimer test would be negative (no fibrin to be broken down) In secondary fibrinolysis, D-dimer test would be positive

Question 56

Therapeutic (Iatrogenic) fibrinolysis

Answer 56

Fibrinolysis induced by the injection of direct plasminogen activators (eg. tPA)

Question 57

Thrombosis

Answer 57

Abnormal formation in circulation of solid, localized masses of fibrin and/or platelets that cause partial or complete blockage of vessels

Question 58

Thromboembolism

Answer 58

Thrombi break away and block smaller vessels

Question 59

3 factors involved in forming a thrombus (Virchow's triad)

Answer 59

Slowed blood flow Hypercoagulability Vessel wall damage

Question 60

Is arterial thrombosis or venous thrombosis more common and why?

Answer 60

Venous thrombosis, because blood flows more slowly through veins than through arteries

Question 61

High risk factors for thrombosis

Answer 61

``` Family history Hypertension Prolonged immobility Older age Male sex Tobacco smoking Obesity ```

Question 62

Inherited disorders that promote thrombosis

Answer 62

Factor V Leiden gene mutation (Protein C resistance) Antithrombin III deficiency Protein C deficiency or protein S deficiency Homocysteinuria Dysfibrinogenemia Abnormal plasminogen Prothrombin G20210A variant

Question 63

Factor V Leiden gene mutation

Answer 63

Protein C resistance Most common cause of increased risk of venous thrombosis Abnormal Factor V molecule is produced that resists the action of activated Protein C -> factor V is inappropriately maintained in an active form which continues to promote coagulation

Question 64

Homocysteinuria

Answer 64

homocysteine (an amino acid that normally gets broken down) is deposited and causes atherosclerosis, adherence of platelets, coagulation and thrombosis