Bleeding Disorders

Question 1

What are the 4 steps to normal hemostasis (clot formation)?

Answer 1

1. Vasoconstriction
2. Platelet plug formation
3. Coagulation cascade to stabilize clot
4. Limit fibrin clot

Question 2

If there is a primary hemostasis disorder that causes excessive bleeding, how is it likely inherited?

Answer 2

Autosomal Dominant
(primary = platelet plug formation)

Question 3

If there is a secondary hemostasis disorder that causes excessive bleeding, where are the bleeds usually located?

Answer 3

Joints - hemarthroses

Question 4

4 types of bleeding disorders?

Answer 4

• Vessel wall abnormalities
• Reduced platelet number
• Reduced platelet function
• Clotting factor abnormalities

Question 5

PT measures?

Answer 5

Extrinsic pathway (tissue factor + FVII)

Question 6

PTT measures?

Answer 6

Intrinsic pathway

Question 7

What is an example of a vessel wall abnormality that leads to excessive bleeding in the periorbital region?

Answer 7

Perivascular amyloid in myeloma

= periorbital bruising (raccoon eyes)

Question 8

< 150K platelets

Answer 8

Thrombocytopenia

Question 9

Symptoms for thrombocytopenia usually manifest at what number of platelets?

Answer 9

< 50K

Question 10

Dangerous spontaneous bleeds with thrombocytopenia can occur when the number of platelets is below?

Answer 10

< 20K

Question 11

What are 3 immune destruction disorders of platelets?

Answer 11

1. HIV-associated thrombocytopenia
2. Drug-induced thrombocytopenia
3. Immune Thrombocytopenic Purpura (ITP)

Question 12

HIV-associated thrombocytopenia suppresses bone marrow by?

Answer 12

Infecting hematopoietic stem cells

Question 13

HIV-associated thrombocytopenia will produce _____ against platelets

Answer 13

Autoantibodies

Question 14

Drug-induced thrombocytopenia via Myelosuppression occurs from?

Answer 14

Chemotherapy, Chloramphenicol and others

Question 15

Drug-induced immune thrombocytopenia occurs from?

Answer 15

Quinidine, Vancomycin, Heparin

Question 16

Heparin induced immune thrombocytopenia involves what cascade of events?

Answer 16

PF4 - Heparin complex activates IgG

• IgG binds to the Fc receptor and activates platelets
• Platelets are degraded by IgG

Question 17

What happens with Immune Thrombocytopenic Purpura (ITP)?

Answer 17

Autoantibodies against platelets bind to platelets

- Macrophages destroy platelets

Question 18

Acute form of Immune Thrombocytopenic Pupura occurs in?

Answer 18

Kids

Question 19

Chronic form of immune thrombocytopenic purpura occurs in?

Answer 19

Young adult women

Question 20

What are the symptoms seen with Immune Thrombocytopenic Purpura?

Answer 20

Petechiae, purpura, thrombocytopenia, platelet antibodies and increased megakaryocytes in marrow

Question 21

Increased Megakaryocytes in the bone marrow could indicate?

Answer 21

Immune Thrombocytopenic Purpura

Question 22

Treatment for Immune Thrombocytopenic Purpura?

Answer 22

Corticosteroids
IVIg
CD20 - rituximab

Question 23

What are 2 Non-immune destruction disorders of platelets?

Answer 23

Thrombotic Thrombocytopenia Purpura (TTP)

Hemolytic Uremic Syndrome

Question 24

Normally, what metalloproteinase converts multimers of vWF to smaller multimers?

Answer 24

ADAMTS13

Question 25

In Thrombotic Thrombocytopenic Purpura, what is missing or inhibited?

Answer 25

ADAMTS13

Question 26

Results of Thrombotic Thrombocytopenic Purpura missing ADAMTS13?

Answer 26

Formation of ultra-large multimers of vWF that initiate aggregation and thrombosis

Question 27

What is the treatment for Thrombotic Thrombocytopenic Purpura?

Answer 27

Plasma exchange therapy to take out autoantibodies for ADAMTS13 and multimers and give ADAMTS13

Question 28

What are the 5 main symptoms of Thrombotic Thrombocytopenic Purpura?

Answer 28

``` Fever Thrombocytopenia MAHA - Microangiopathic Hemolytic Anemia Renal failure Neurologic Defects ```

Question 29

What toxin is associated with Hemolytic Uremic Syndrome?

Answer 29

Shiga-like toxin elaborated by E.coli 0157 H7

Question 30

Patients with Hemolytic Uremic Syndrome present first with?

Answer 30

Bloody diarrhea

Question 31

Patients with Hemolytic Uremic Syndrome present with what 3 main symptoms?

Answer 31

MAHA Thrombocytopenia Renal failure

Question 32

What is MAHA?

Answer 32

Microangiopathic Hemolytic Anemia | = Platelet aggregation causes passing RBCs to shear and create schistocytes

Question 33

What 2 platelet destruction disorders involve MAHA?

Answer 33

Thrombotic Thombocytopenic Purpura Hemolytic Uremic Syndrome = when platelet aggregation causes passing RBCs to shear and create schistocytes

Question 34

What are 3 inherited disorders due to defective platelet function?

Answer 34

Bernard - soulier Glanzmann Thrombasthenia Storage pool disorders

Question 35

What are 2 acquired disorders due to defective platelet function?

Answer 35

Aspirin use | Uremia

Question 36

No adhesion, lack of GP1b

Answer 36

Bernard - Soulier

Question 37

No aggregation, lack of GP2b3a

Answer 37

Glanzmann Thrombasthenia

Question 38

No release of dense granules

Answer 38

Storage pool disorders

Question 39

No release of alpha granules

Answer 39

Grey platelet syndrome

Question 40

Platelet vs. coagulation disorders - depth of bleed

Answer 40

``` Platelet = superficial mucosal bleeding Coagulation = deep soft tissue bleeding ```

Question 41

Platelet vs. coagulation disorders - petechiae?

Answer 41

``` Platelet = petechiae present Coagulation = Minimal petechiae ```

Question 42

Platelet vs. coagulation disorders - bruise size

Answer 42

``` Platelet = small, superficial bruises Coagulation = Large, deep bruises ```

Question 43

Platelet vs. coagulation disorders - hemarthroses?

Answer 43

``` Platelet = rare hemarthroses Coagulation = common hemarthroses ```

Question 44

Platelet vs. coagulation disorders - time to bleed?

Answer 44

``` Platelet = bleeding after minor cuts Coagulation = delayed bleeding after cuts ```

Question 45

Why is it important for circulating vWF to join factor VIII?

Answer 45

It takes VIII to the site of the platelet plug so that factor VIII can activate the coagulation cascade and further stabilize the clot

Question 46

vWF disease type 1

Answer 46

Decreased secretion of vWF

Question 47

vWF disease type 1c

Answer 47

Increased clearance of vWF

Question 48

vWF disease type 3

Answer 48

SEVERE decreased secretion of vWF

Question 49

vWF disease type 2

Answer 49

lack of appropriate interaction with ligands

Question 50

vWF disease type 2a

Answer 50

Lack of multimer assembly

Question 51

Hemophilia A involves what coagulation factor?

Answer 51

VIII

Question 52

Hemophilia B involves what coagulation factor?

Answer 52

IX

Question 53

How are both Hemophilia A and B inherited?

Answer 53

X-linked recessive

Question 54

Overall summary of Disseminated Intravascular Coagulation?

Answer 54

Coagulation activates Thrombi form Everything gets used up Bleed occurs

Question 55

With DIC, tissue injury, sepsis and conception products cause what to be release?

Answer 55

Tissue factor

Question 56

The release of tissue factor causes what with DIC?

Answer 56

Widespread thrombosis

Question 57

With DIC, widespread thrombosis causes what main things?

Answer 57

1. Consumption of platelets and clotting factors | 2. Proteolysis of clotting factors

Question 58

Consumption of platelets and clotting factors with DIC will cause ____ platelets and _____ PT/PTT

Answer 58

Decreased platelets | Increased PT/PTT

Question 59

Proteolysis of clotting factors with DIC will cause increased?

Answer 59

D-dimer

Question 60

What is the end result of DIC?

Answer 60

BLEEDING