Bleeding Disorders Flashcards
Platelet bleeding
Superificial
Petechiae
Spontaneous
Factor bleeding
Deep (joints)
Trauma
Big Bleeds
Von Willebrand Disease - must knows
Most common hereditary bleeding disorder (NOT factor)
Autosomal dominant
vW factor decreased or abnormal
Variable severity
What is vWF
Huge multimeric protein made by megakaryocytes and endothelial cells
Glues platelets to subendothelium
Carries factor VIII
Type 1 vWF
Decreased vWF (70% of cases)
Type 2 vWF
Abnormal vWF (25% of cases)
Type 3 vWF
No vWF (5%)
Symptoms of vWF disease
Mucosal bleeding
Deep joint bleeding (severe cases)
Lab tests in vWF disease
Bleeding time: prolonged PTT: prolonged (corrects with mixing study) INR: normal vWF: level decreased (normal in type 2) Platelet aggregation studies abnormal
What binds vWF?
GP Ib (membrane)
Treatment of vWF disease
DDAVP (raise VIII and vWF levels)
Cryoprecipitate (contains vWF and VIII)
Factor VIII
Hemophilia A is a ______ genetic disorder
X linked
Dads affected with hemophilia A
will have carrier daughters
Moms who are carriers of hemophilia A
Son may have disease, daugher may carry
Hemophilia A
Most common FACTOR deficiency
Factor VIII decreased
Symptoms of Hemophilia A
Severity depends on amount of VIII
Typical ‘factor’ bleeding (deep joint bleeding, prolonged bleeding after dental work)
Rarely - mucosal hemhorrhage
Lab tests in hemophilia A
INR, TT, Platelet count, bleeding time: NORMAL
PTT: prolonged (corrects with mixing)
Factor VIII assays: abnormal
DNA studies: abnormal
Treatment of Hemophilia A
DDAVP
Factor VIII
Hemophilia B
Factor IX deficiency
Less common than Hemophilia A
Same inheritance pattern (x linked)
Same clinical and laboratory findings
Factor XI deficiency
Bleeding only after trauma (rare)
Factor XIII deficiency
severe neonatal bleeding (no cross links, can kill you)
Hereditary platelet disorders (4)
- Bernard Soulier Syndrome
- Glanzmann Thrombasthenia
- Gray Platelet Syndrome
- Delta Granule Deficiency
Bernard Soulier Syndrome
Abnormal Ib (binds vWF)
Abnormal adhesion
Big platelets
Severe Bleeding
Glanzmann Thrombasthenia
No IIb-IIIa (binds fibrinogen)
No aggregation
Severe bleeding
Gray Platelet syndrome
No a-granules - why gray
Big, empty platelets
Mild bleeding
Delta granule deficiency
No d-granules
Can be part of syndrome (Chediak-Higashi)
Acquired Bleeding disorders (2)
- DIC
2. Idiopathic Thrombocyopenic Purpura
Disseminated Intravascular Coagulation (DIC)
Lots of underlying disorders
Something triggers coagulation, causing thrombosis
Platelets and factors get used up, cause bleeding
Microangiopathic hemolytic anemia
Causes of DIC
Dumpers and Rippers
Dumpers
OB complications
Adenocarcinoma
AML-3 (granules are pro coag)
Rippers
Bacterial sepsis
Trauma
Burns
Vasculitis
What are the big 4 for DIC (hint.. MOST)
Malignancy
Obstetric Complications
Sepsis
Trauma
Symptoms of DIC
Can be nsidious or fulminant
Multisystem disease
Thrombosis and or bleeding
Lab tests in DIC
INR, PTT, TT prolonged
FDPs increased
Fibrinogen decreased
Treatment of DIC
Treat underlying disorder
Support with blood products
Idiopathic Thrombocytopenic Purpura
Antiplatelet antibodies
Acute vs chronic
Diagnosis of exclusion
Steroids or splenectomy
Pathogenesis of ITP
Autoantibodies to GP IIb-IIa or Ib
Bind to platelets
Macrophages eat platelets
Two kinds of ITP
Chronic or Acute
Chronic ITP
Adult women
Primary or secondary
Insidious - nosebleeds, easy bruising
Danger - bleeding into brain
Acute ITP
Children
Abrupt following illness
Usually self limiting
May become chronic
Lab tests in ITP
- Signs of platelet destruction : thrombocytopenia, normal/increased megakaryocytes, big platelets
- INR/PTT normal
- No specific diagnostic test
Thrombocytopenia
Caused by many things - aplastic anemia, bone marrow replacement, big speen, consumptive processes (DIC, TTP, HUS), drugs
Treatment of ITP
glucocorticoids
splenectomy
IV immunoglobulin
Thrombotic microangiopathies
All have thrombi, thrombocytopenia and MAHA
Include TTP and HUS
Hard to distinguish from TTP from HUS
in thrombotic microangiopathies something triggers ______
platelet aactivation
Thrombotic Thrombocytopenic Purpora
Pentad: MAHA, thrombocytopenia, renal failure, fever, neurologic defects
TTP deficiency
ADAMTS13
Big vWF aren’t cleaved, trap platelets
How do deal with TTP
plasmapheresis or plasma infusions
Brief pathogenesis of TTP
Just released vWF is unusually large (UL), causes vWF to aggregate. Usually ADAMTS13 cleaves into less active bits. TTP is deficient in ADAMTS13
Clinical findings of TTP
Hematuria, jaundice (MAHA) Bleeding, brusing (thrombocytopenia) Fever Decreased urine output (Renal Failure) Bizarre behavior (Neurological defects)
Treatment of TTP
Acquired: plasmapheresis
Hereditary: Plasma infusions
Hemolytic Uremic Syndrome
MAHA and thrombocytopenia
Epidemic (e coli) vs. non epidemic
Toxin? damages epithelium
Treat supportively
Pathogenesis of HUS - epidemic
E coli O157:H7 (raw hamburger)
Makes nasty toxin
Injures endothelial cells
Pathogenesis of HUS - non epiodemic
Defect in complement factor H
Inherited or acquired
Clinical findings in HUS - epidemic
Children and elderly
Bloodly diarrhea, renal failure
Fatal in 5% of cases
Clinical findings in HUS - non epidemic
Renal failure
Relapsing remitting course
Fatal in 50% of cases
Treatment of HUS
Supportive Care
Dialysis
Not antibiotics (increase toxin release)
