Bleeding Disorders - Krafts

Question 1

What are the Hereditary Bleeding Disorders?

Answer 1

von Willebrrand Disease
Hemophilia A and B
Hereditary Platelet Disorder

Question 2

What are the Acquired Bleeding Disorders?

Answer 2

DIC
ITP
TTP/HUS

Question 3

What factors are seen when the disorder is due to platelet bleeding?

Answer 3

Superficial (skin)
Petechiae
Spontaneous - no accident

Question 4

What factors are seen when the disorder is due to factor bleeding?

Answer 4

Deep (joints)
Big Bleeds
Trauma

Question 5

What are the characteristics of von Willebrand Disease?

Answer 5

Most common hereditary bleeding
Autosomal Dominant
von Willebrand factor decreased
Variable severity

Question 6

What is the clinical finding of Type 1 Von Willebrand Disease?

Answer 6

Decreased vWF

Question 7

What is the clinical finding of Type 2 Von Willebrand Disease?

Answer 7

Abnormal vWF

Question 8

What is the clinical finding of Type 3 Von Willebrand Disease?

Answer 8

No vWF

Question 9

What is von Willebrand Factor?

Answer 9

Huge multimeric protein made by Megakaryocytes and Endothelial cells
Glues platelets to endothelium

Question 10

What factor does von Willebrand Factor carry?

Answer 10

Factor VIII (Intrinsic Pathway)

Question 11

What are the symptoms of von Willebrand Disease?

Answer 11

Most patients are asymptomatic
Mucosal bleeding (most)
Deep joint bleeding (severe)

Question 12

What lab tests would be checked and what would the values be in von Willebrand Disease?

Answer 12

Bleeding Time = prolonged
PTT = prolonged 
Mixing Study = corrected
INR = Normal
vWF level = decreased (except in Type 2)
Platelet aggregation = abnormal

Question 13

What membrane bound proteins are in the platelet?

Answer 13

Phospholipids activate coag factors
GP Ia binds collagen
GP Ib binds vWF
GP IIb-IIIa binds fibrinogen

Question 14

What makes platelets express the GP Ib membrane bound protein?

Answer 14

Ristocetin (does not work in vWD = missing vWF)

Question 15

What is the treatment for Von Willebrand Disease?

Answer 15

DDAVP = raises factor VIII and vWF levels
Cryoprecipitate = contains vWF and VIII
Factor VIII

Question 16

What are the genetic characteristics of Hemophilia inheritance?

Answer 16

X-Linked Recessive Disorder

~30% are random mutations

Question 17

What are the characteristics of Hemophilia A?

Answer 17

Most common factor deficiency

Factor VIII level decreased

Question 18

What are the symptoms of Hemophilia A?

Answer 18

Typical “Factor” Bleeding with Deep Joint bleeding or prolonged bleeding after dental work (preceding trauma)
Rarely = Mucosal Hemorrhage or Petechiae
Severity depends on amount of VIII

Question 19

What lab tests are used to diagnose Hemophilia A and what are the expected values?

Answer 19

Normal: INR, TT, Platelet Count, Bleeding Time
PTT = prolonged
Mixing Study = corrected
Factor VIII assay and DNA studies = abnormal

Question 20

What is the treatment for Hemophilia A?

Answer 20

DDAVP

Factor VIII

Question 21

What are the characteristics of Hemophilia B?

Answer 21

Factor IX decreased
Less common than Hemophilia A
X-Linked Recessive Disorder
Same clinical and lab findings

Question 22

What happens with a factor XI deficiency?

Answer 22

Bleeding only after trauma

Question 23

What happens with a factor XIII deficiency?

Answer 23

Severe neonatal bleeding

Question 24

What are the Hereditary Platelet Disorders?

Answer 24

Bernard-Soulier Syndrome
Glanzmann Thrombasthenia
Gray Platelet Syndrome
Delta-Granule Deficiency

Question 25

What are the characteristics of Bernard-Soulier Syndrome?

Answer 25

Abnormal GP Ib Abnormal adhesion Big platelets Severe bleeding

Question 26

What are the characteristics for Glanzmann Thrombasthenia?

Answer 26

No GP IIb-IIIa fibrinogen receptor No aggregation Severe bleeding

Question 27

What are the characteristics for Gray Platelet Syndrome?

Answer 27

No alpha granules Empty, Big platelets Mild bleeding

Question 28

What are the characteristics for delta-Granule Deficiency?

Answer 28

No delta granules | Associated with Chediak-Higashi syndrome

Question 29

What are the characteristics of Disseminated Intravascular Coagulation (DIC)?

Answer 29

Something triggers coagulation causing thrombosis | Platelets and factors get used up causing bleeding

Question 30

What is the major issue in DIC?

Answer 30

Microangiopathic Hemolytic Anemia

Question 31

What are the "Dumper" causes of DIC?

Answer 31

Dumper = coagulation substances are dumped into the blood Obstetric complications Adenocarcinoma Acute Promyelocytic Leukemia

Question 32

What are the "Ripper" causes of DIC?

Answer 32

``` Ripper = Anything that will damage the endothelium Bacterial Sepsis Trauma Burns Vasculitis ```

Question 33

What are the top 4 causes of DIC?

Answer 33

``` MOST common causes of DIC: Malignancy Obstetric Complications Sepsis Trauma ```

Question 34

What are the symptoms of DIC?

Answer 34

Insidious or fulminant Multi-system disease Thrombosis and/or Bleeding

Question 35

What lab tests are used to diagnose DIC and what are the expected values?

Answer 35

Prolonged INR, PTT, TT Increased FDPs Decreased Fibrinogen

Question 36

What is the treatment of DIC?

Answer 36

Treat underlying disorder while supporting with blood products

Question 37

What are the characteristics of Idiopathic Throbocytopenic Purpura?

Answer 37

Antiplatelet Antibodies Acute vs. Chronic Diagnosis of Exclusion

Question 38

What is the treatment of Idiopathic Thrombocytopenic Purpura?

Answer 38

Steroids (Glucocorticoids) IVIG Splenectomy

Question 39

What is the pathogenesis of Idiopathic Thrombocytopenic Purpura?

Answer 39

Autoantibodies to GP IIb-IIIa or GP Ib Binds to Platelets Splenic macrophages eat platelets

Question 40

What are the characteristics of Chronic Idiopathic Thrombocytopenic Purpura?

Answer 40

Primary or Secondary Adult Women Insidious: Nosebleeds, Easy Bruising DANGER: Bleeding in Brain

Question 41

What are the characteristics of Acute Idiopathic Thrombocytopenic Purpura?

Answer 41

Children Abrupt (follows viral illness) Usually self-limiting May become chronic

Question 42

What lab tests are used to diagnose Idiopathic Thrombocytopenic Purpura and what are the expected values?

Answer 42

``` Normal INR/PTT Signs of platelet destruction: -Thrombocytopenia -Normal/Increased megakaryocytes -Big Platelets ```

Question 43

What are some other causes of Throbocytopenia besides ITP?

Answer 43

``` Aplastic anemia Bone marrow replacement Large spleen Consumptive processes (DIC, TTP, HUS) Drugs ```

Question 44

What are the characteristics of Thrombotic Microangiopathies (TTP and HUS)?

Answer 44

Thrombi, Throbocytopenia, AND MAHA | Something triggers Platelet Activation

Question 45

What are the symptoms of Thrombotic Thrombocytopenic Purpura (TTP)?

Answer 45

MAHA, Thrombocytopenia, Fever, Neurologic Defects, Renal Failure

Question 46

What is the deficiency associated with TTP?

Answer 46

ADAMTS13

Question 47

What is the treatment of TTP?

Answer 47

``` Plasmapheresis (Acquired TTP) Plasma infusions (Hereditary TTP) ```

Question 48

What is the pathogenesis of TTP?

Answer 48

Big vWF multimers that trap platelets

Question 49

What is the normal function of ADAMTS13?

Answer 49

To cleave unusually large vWF into less active bits

Question 50

What are the clinical findings of TTP?

Answer 50

``` Hematuria, Jaundice (MAHA) Bleeding, Bruising (Thrombocytopenia) Fever Bizarre Behavior (Neurologic Deficits) Decreased Urine Output (Renal Failure) ```

Question 51

What is the most common pathogenesis of Hemolytic Uremic Syndrome (HUS)?

Answer 51

Epidemic usually caused by E. coli toxin-induced injury to endothelial cells

Question 52

What are the characteristics of HUS?

Answer 52

MAHA and Thrombocytopenia | Toxin that damages endothelium

Question 53

What is the pathogenesis of Non-Epidemic HUS?

Answer 53

Defect in complement factor H | Inherited or Acquired

Question 54

What are the clinical findings of Epidemic HUS?

Answer 54

Children/Elderly | Bloody diarrhea, then renal failure

Question 55

What are the clinical findings of Non-Epidemic HUS?

Answer 55

Renal Failure Relapsing-Remitting Course Fatal in 50% of cases

Question 56

What is the treatment of HUS?

Answer 56

Supportive Care | Dialysis