Bleeding Disorders Flashcards
Clinical features platelet bleeding
Superficial (skin)
Petechiae (bigger areas = purpura)
Spontaneous
Clinical features factor bleeding
Deep (joints)
Big bleeds
Trauma
Von Willebrand Disease TYMK
Most common hereditary bleeding disorder
Autosomal dominant
vW factor decreased (or abnormal)
Variable severity
most common hereditary bleeding disorder
VW disease
most common factor disorder
hemophilia (VW is not considered a factor disorder)
inheritance VWD
Autosomal dominant
von willebrand factor
Huge multimeric protein
Decreased or abnormal in vW disease
von willebrand factor function
Glues platelets to subendothelium
Carries factor VIII
von willebrand factor made by
Made by megs and endothelial cells
von willebrand disease is a platelet/factor disorder
platelet - but if really bad, because carries factor VIII, can look like a factor disorder as well
Types of vW disease
Type 1 (70%): Decreased vWF Type 2 (25%): abnormal vWF Type3 (5%): no vWF
symptoms of vW disease
Mucosal bleeding in most patients
Deep joint bleeding in severe cases
Lab Tests in Von Willebrand Disease
Bleeding time: prolonged PTT: prolonged (severe) (“corrects” with mixing study) INR: normal vWF level decreased (normal in type 2) Platelet aggregation studies abnormal
What binds to vWF
GP Ib on membrane of platelet (glycoprotein)
what doesn’t wF disease work with in platelet aggregation test?
Ristocetin
treatment of vW disease
DDAVP (raises VIII and vWF levels)
Cryoprecipitate (contains vWF and VIII)
Factor VIII
Hemophilia A TYMK
Most common factor deficiency
X-linked recessive in most cases
(30% are random mutations)
Factor VIII level decreased
Variable amount of “factor” bleedingMost common factor deficiency
Hem A
Hem A inheritance
X-linked recessive
what factor is decreased in Hem a
Factor VIII
Symptoms Hem A
Severity depends on amount of VIII Typical “factor” bleeding deep joint bleeding prolonged bleeding after dental work Rarely, mucosal hemorrhage
Lab Tests in Hem A
INR, TT, platelet count, bleeding time: normal (these are platelet issues, hem is a fibrin issue)
PTT: prolonged (“corrects” with mixing study)
Factor VIII assays: abnormal
DNA studies: abnormal
Treatment Hem A
DDAVP (release stores of vWF and VIII)
Factor VIII
Hem B TYMK
Factor IX level decreased
Much less common than hemophilia A
Same inheritance pattern
Same clinical and laboratory findings
what factor decreased in Hem B
Factor IX
Inheritance pattern Hem B
x-linked recessive (30% lab findings)
clinical findings Hem B
Severity depends on amount of VIII Typical “factor” bleeding deep joint bleeding prolonged bleeding after dental work Rarely, mucosal hemorrhage
lab tests Hem B
INR, TT, platelet count, bleeding time: normal (these are platelet issues, hem is a fibrin issue)
PTT: prolonged (“corrects” with mixing study)
Factor VIII assays: abnormal
DNA studies: abnormal
XI deficiency
bleeding only after trauma
XIII deficiency
severe neonatal bleeding
Bernard-Soulier Syndrome
Abnormal Ib (binds vWF)
Abnormal adhesion
Big platelets
Severe bleeding
Glanzmann Thrombasthenia
No IIb-IIIa (what binds fibrinogen)
No aggregation
Severe bleeding
Gray Platelet Syndrome
No alpha granules
Big, empty platelets
Mild bleeding
Delta granule deficiency
No delta granules
Can be part of syndrome (e.g., Chediak-Higashi)
alpha granules
fibrinogen, vWF
delta granules
serotonin, ADP, ca2+
DIC TYMK
Lots of underlying disorders
Something triggers coagulation, causing thrombosis
Platelets and factors get used up, causing bleeding
Microangiopathic hemolytic anemia
Causes of DIC can be separated into
dumpers (into vascular system to set off cascade)
rippers (rip up endothelium)
DIC causes: Dumpers
Obstetric complications
Adenocarcinoma
Acute promyelocytic leukemia
DIC causes: Rippers
Bacterial sepsis
Trauma
Burns
Vasculitis
Causes of DIC to remember
Malignancy OB complications Sepsis Trauma (MOST)
Symptoms of DIC
Insidious or fulminant
Multi-system 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 thrombocytopenia Purpura TYMK
Antiplatelet antibodies Acute vs. chronic Diagnosis of exclusion Steroids or splenectomy Remember how different this is from DIC
Pathogenesis of ITP
Autoantibodies to platelets = GP IIb-IIIa or Ib
Bind to platelets (yummy!)
Splenic macrophages eat platelets
two kinds of itp
chronic
acute
chronic ITP
Adult women
Primary or secondary
Insidious: nosebleeds, easy bruising
Danger: bleeding into brain
acute ITP
Children
Abrupt; follows viral illness
Usually self-limiting
May become chronic
Lab tests ITP
Signs of platelet destruction: - thrombocytopenia - normal/increased megakaryocytes - big platelets INR/PTT normal No specific (ab) diagnostic test for ITP
Other causes of thrombocytopenia
Aplastic anemia Bone marrow replacement Big spleen Consumptive processes (DIC, TTP, HUS) Drugs
tx of ITP
Glucocorticoids
Splenectomy
Intravenous immunoglobulin
Thrombotic microangiopathies all have
thrombi, thrombocytopenia, and MAH
Thrombotic microangiopathies include
TTP and HUS (can be hard to distinguish)
Different from DIC
thrombotic microangiopathies = something triggers _______
platelet activation
Thrombotic thrombocytopenic purpura TYMK
Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure
Deficiency of ADAMTS13
Big vWF multimers trap platelets
Plasmapheresis or plasma infusions
pentad TTP
MAHA, thrombocytopenia, fever, neurologic defects, renal failure
TTP deficiency in
ADAMTS13
Pathogenesis TTP
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
Clinical findings in TTP
Hematuria, jaundice (MAHA) Bleeding, bruising (thrombocytopenia) Fever Bizarre behavior (neurologic deficits) Decreased urine output (renal failure)
Treatment of TTP
Acquired TTP: plasmapheresis
Hereditary TTP: plasma infusions
Hemolytic Uremic Syndrome TYMK
MAHA and thrombocytopenia
Epidemic (E. coli) vs. non-epidemic
Toxin (or ?) damages endothelium
Treat supportively
Pathogenesis of HUS has 2 main causes
Epidemic
Non-epidemic
HUS epidemic pathogenesis
E. coli O157:H7 (raw hamburger)
Makes nasty toxin (shiga or shiga-like)
Injures endothelial cells
HUS non-epidemic pathogenesis
Defect in complement factor H (protective)
Inherited or acquired
How does this activate platelets?
HUS epidemic associated with usually
E. coli O157:H7
Clinical findings in HUS epidemic
Children, elderly
Bloody diarrhea, then renal failure
Dont give Abx (expose toxin)
Fatal in 5% of cases
Clinical findings in HUS non-epidemic
Renal failure
Relapsing-remitting course
Fatal in 50% of cases
Treatment HUS
Supportive care
Dialysis
NOT antibiotics (may increase toxin release!)
