Krafts- Friday Bleeding Disorders

Question 1

Platelet bleeding: Clinical Presentation

Answer 1

Superficial (skin)
Petechiae
Spontaneous
often from mucosal membranes (eg. nose bleed)

Question 2

Factor bleeding: Clinical Presentation

Answer 2

Deep (joints)
Big bleeds
Trauma

Question 3

Petechiae

Answer 3

spotted red dots

blood in the skin outside the arteries and veins

Question 4

Purpura

Answer 4

the combination of a lot of petechiae into one are so it looks like a continuous bleed

Question 5

von Willebrand disease: Things you must know

Answer 5

Most common hereditary bleeding disorder
Autosomal dominant
vW factor decreased (or abnormal)
Variable severity

Question 6

What’s von Willebrand Factor?

Answer 6

Huge multimeric protein
Made by megakaryocytes and endothelial cells
*Glues platelets to endothelium*
Carries factor VIII
Decreased or abnormal in vW disease

Question 7

Types of Von Willebrand Disease

Answer 7

Type 1 (70%): decreased vWF
Type 2 (25%):  abnormal vWF
Type 3 (5%):  no vWF

Question 8

Symptoms of Von Willebrand Disease

Answer 8

Mucosal bleeding in most patients

Deep joint bleeding in severe cases

Question 9

Lab Tests in Von Willebrand Disease

Answer 9

Bleeding time: prolonged
PTT: prolonged (“corrects” with mixing study) 
INR: normal
vWF level decreased (normal in type 2)
Platelet aggregation studies abnormal

Question 10

GP Ib binds what

Answer 10

binds vWF

ristocetin –>

Question 11

ristocetin

Answer 11

is an old antibiotic that makes you express high levels of GP Ib from your platelets.
Helps dx vWF disease because this will soak up the little vWF that the patient has in their blood

Question 12

Treatment of Von Willebrand Disease

Answer 12

DDAVP (raises VIII and vWF levels) but you need to already be making some (won’t work for type III)

Cryoprecipitate (contains vWF and VIII)

Factor VIII

but try to avoid giving anything due to bleeding issues, these are if the patient isn’t doing well

Question 13

Hemophilia A: Things you must know

Answer 13

Most common factor deficiency

X-linked recessive in most cases (30% are spontaneous mutations)

Factor VIII level decreased

Variable amount of “factor” bleeding

Question 14

Symptoms of Hemophilia A

Answer 14

Severity depends on amount of VIII

Typical “factor” bleeding

deep joint bleeding

prolonged bleeding after dental work

Rarely, mucosal hemorrhage

Question 15

Lab Tests in Hemophilia A

Answer 15

INR, TT, platelet count, bleeding time: normal
PTT: prolonged (“corrects” with mixing study)
Factor VIII assays: abnormal
DNA studies: abnormal

Question 16

Treatment of Hemophilia A

Answer 16

DDAVP

Factor VIII

Question 17

Hemophilia B: Things you must know

Answer 17

Factor IX level decreased
Much less common than hemophilia A
Same inheritance pattern as type A
Same clinical and laboratory findings as type A

Question 18

Factor XI deficiency

Answer 18

bleeding only after trauma

super rare

Question 19

Factor XIII deficiency:

Answer 19

severe neonatal bleeding

super rare

Question 20

Bernard-Soulier Syndrome

Answer 20

Abnormal factor Ib
Abnormal adhesion
Big platelets
Severe bleeding

Question 21

Glanzmann Thrombasthenia

Answer 21

No factor IIb-IIIa
No aggregation
Severe bleeding

Question 22

Gray Platelet Syndrome

Answer 22

No alpha granules
Big, empty platelets
Mild bleeding

Question 23

Delta Granule Deficiency

Answer 23

No Delta granules (never would have guessed)

Can be part of syndrome (e.g., Chediak-Higashi)

Question 24

Disseminated Intravascular Coagulation: Thinks you must know

Answer 24

Lots of underlying disorders
Something triggers coagulation, causing thrombosis
Platelets and factors get used up, causing bleeding
Microangiopathic hemolytic anemia

Question 25

Causes of DIC

Answer 25

Dumpers: *Obstetric complications, Adenocarcinoma, Acute promyelocytic leukemia Rippers: *Bacterial sepsis, *Trauma, Burns, Vasculitis

Question 26

Symptoms of DIC

Answer 26

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

Question 27

Lab Tests in DIC

Answer 27

INR, PTT, TT prolonged FDPs: increased Fibrinogen: decreased *All of them have to be this way, no one Dx test

Question 28

Treatment of DIC

Answer 28

Treat underlying disorder | Support with blood products

Question 29

Idiopathic Thrombocytopenic Purpura: Things you must know

Answer 29

Antiplatelet antibodies Acute vs. chronic Diagnosis of exclusion Steroids or splenectomy

Question 30

Pathogenesis of ITP

Answer 30

Autoantibodies to GP IIb-IIIa or Ib Bind to platelets (yummy!) Splenic macrophages eat platelets

Question 31

Two Kinds of ITP: Tell me about chronic type

Answer 31

``` Chronic Adult women (usually young adult women) Primary or secondary Insidious: nosebleeds, easy bruising Danger: bleeding into brain ```

Question 32

Two Kinds of ITP: Tell me about acute type

Answer 32

``` Acute Children Abrupt; follows viral illness Usually self-limiting May become chronic ```

Question 33

Lab Tests in ITP

Answer 33

Signs of platelet destruction: thrombocytopenia normal/increased megakaryocytes big platelets INR/PTT normal No specific diagnostic test for ITP

Question 34

Other Causes of Thrombocytopenia besides ITP

Answer 34

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

Question 35

Treatment of ITP

Answer 35

Glucocorticoids Intravenous immunoglobulin Splenectomy (site of destruction so it helps)

Question 36

Thrombotic Microangiopathies

Answer 36

``` All have thrombi, thrombocytopenia, and MAHA Include TTP and HUS Can be hard to distinguish TTP from HUS Something triggers platelet activation Different from DIC! ```

Question 37

Thrombotic Thrombocytopenic Purpura: things to know

Answer 37

Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure Deficiency of ADAMTS13 Big vWF multimers trap platelets Plasmapheresis or plasma infusions

Question 38

Pathogenesis of TTP

Answer 38

Just-released vWF is unusually large (UL) UL vWF causes platelet aggregation ADAMTS13 cleaves UL vWF into less active bits! TTP is due to ADAMTS13 deficiency

Question 39

Clinical Findings in TTP

Answer 39

``` Hematuria, jaundice (MAHA) Bleeding, bruising (thrombocytopenia) Fever Bizarre behavior (neurologic deficits) Decreased urine output (renal failure) ```

Question 40

Treatment of TTP

Answer 40

Acquired TTP: plasmapheresis | Hereditary TTP: plasma infusions

Question 41

Hemolytic Uremic Syndrome: things you must know

Answer 41

MAHA and thrombocytopenia Epidemic (E. coli) vs. non-epidemic Toxin (or ?) damages endothelium Treat supportively

Question 42

Pathogenesis of HUS

Answer 42

Epidemic (more common) E. coli O157:H7 (raw hamburger) Makes nasty toxin Injures endothelial cells Non-epidemic (rare) Defect in complement factor H Inherited or acquired

Question 43

Clinical Findings in HUS

Answer 43

Epidemic: Children, elderly Bloody diarrhea, then renal failure Fatal in 5% of cases Non-epidemic: Renal failure Relapsing-remitting course Fatal in 50% of cases

Question 44

Treatment of HUS

Answer 44

Supportive care Dialysis NOT antibiotics (may increase toxin release!)