Platelet bleeding: Clinical Presentation
Superficial (skin)
Petechiae
Spontaneous
often from mucosal membranes (eg. nose bleed)
Factor bleeding: Clinical Presentation
Deep (joints)
Big bleeds
Trauma
Petechiae
spotted red dots
blood in the skin outside the arteries and veins
Purpura
the combination of a lot of petechiae into one are so it looks like a continuous bleed
von Willebrand disease: Things you must know
Most common hereditary bleeding disorder
Autosomal dominant
vW factor decreased (or abnormal)
Variable severity
What’s von Willebrand Factor?
Huge multimeric protein Made by megakaryocytes and endothelial cells *Glues platelets to endothelium* Carries factor VIII Decreased or abnormal in vW disease
Types of Von Willebrand Disease
Type 1 (70%): decreased vWF Type 2 (25%): abnormal vWF Type 3 (5%): no vWF
Symptoms of Von Willebrand Disease
Mucosal bleeding in most patients
Deep joint bleeding in severe cases
Lab Tests in Von Willebrand Disease
Bleeding time: prolonged PTT: prolonged (“corrects” with mixing study) INR: normal vWF level decreased (normal in type 2) Platelet aggregation studies abnormal
GP Ib binds what
binds vWF
ristocetin –>
ristocetin
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
Treatment of Von Willebrand Disease
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
Hemophilia A: Things you must know
Most common factor deficiency
X-linked recessive in most cases (30% are spontaneous mutations)
Factor VIII level decreased
Variable amount of “factor” bleeding
Symptoms of Hemophilia A
Severity depends on amount of VIII
Typical “factor” bleeding
deep joint bleeding
prolonged bleeding after dental work
Rarely, mucosal hemorrhage
Lab Tests in Hemophilia A
INR, TT, platelet count, bleeding time: normal
PTT: prolonged (“corrects” with mixing study)
Factor VIII assays: abnormal
DNA studies: abnormal
Treatment of Hemophilia A
DDAVP
Factor VIII
Hemophilia B: Things you must know
Factor IX level decreased
Much less common than hemophilia A
Same inheritance pattern as type A
Same clinical and laboratory findings as type A
Factor XI deficiency
bleeding only after trauma
super rare
Factor XIII deficiency:
severe neonatal bleeding
super rare
Bernard-Soulier Syndrome
Abnormal factor Ib
Abnormal adhesion
Big platelets
Severe bleeding
Glanzmann Thrombasthenia
No factor IIb-IIIa
No aggregation
Severe bleeding
Gray Platelet Syndrome
No alpha granules
Big, empty platelets
Mild bleeding
Delta Granule Deficiency
No Delta granules (never would have guessed)
Can be part of syndrome (e.g., Chediak-Higashi)
Disseminated Intravascular Coagulation: Thinks you must know
Lots of underlying disorders
Something triggers coagulation, causing thrombosis
Platelets and factors get used up, causing bleeding
Microangiopathic hemolytic anemia
Causes of DIC
Dumpers: *Obstetric complications, Adenocarcinoma, Acute promyelocytic leukemia
Rippers: *Bacterial sepsis, *Trauma, Burns, Vasculitis
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
*All of them have to be this way, no one Dx test
Treatment of DIC
Treat underlying disorder
Support with blood products
Idiopathic Thrombocytopenic Purpura: Things you must know
Antiplatelet antibodies
Acute vs. chronic
Diagnosis of exclusion
Steroids or splenectomy
Pathogenesis of ITP
Autoantibodies to GP IIb-IIIa or Ib
Bind to platelets (yummy!)
Splenic macrophages eat platelets
Two Kinds of ITP: Tell me about chronic type
Chronic Adult women (usually young adult women) Primary or secondary Insidious: nosebleeds, easy bruising Danger: bleeding into brain
Two Kinds of ITP: Tell me about acute type
Acute Children Abrupt; follows viral 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 for ITP
Other Causes of Thrombocytopenia besides ITP
Aplastic anemia Bone marrow replacement Big spleen Consumptive processes (DIC, TTP, HUS) Drugs
Treatment of ITP
Glucocorticoids
Intravenous immunoglobulin
Splenectomy (site of destruction so it helps)
Thrombotic Microangiopathies
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!
Thrombotic Thrombocytopenic Purpura: things to know
Pentad: MAHA, thrombocytopenia, fever, neurologic defects, renal failure
Deficiency of ADAMTS13
Big vWF multimers trap platelets
Plasmapheresis or plasma infusions
Pathogenesis of 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: things you must know
MAHA and thrombocytopenia
Epidemic (E. coli) vs. non-epidemic
Toxin (or ?) damages endothelium
Treat supportively
Pathogenesis of HUS
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
Clinical Findings in HUS
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
Treatment of HUS
Supportive care
Dialysis
NOT antibiotics (may increase toxin release!)