Conditions Flashcards
Primary hemostasis: clinical features (+most common?)
Mucosal and skin bleeding, eg:
- epistaxis (most common)
- hemoptysis, GI bleeding, hematuria, menorrhagia
Primary hemostasis: severe, can’t miss complication?
Intracranial bleeding
Idiopathic thrombocytopenic purpura (ITP): definition? epi?
Splenic autoantibodies (IgG) against platelet antigens causing thrombocytopenia
Most common cause of thrombocytopenia in adults and children
ITP: presentation and course in children
Acute form, presents weeks after viral infection or immunization
Self-limited, resolves within weeks
ITP: presentation and course in adults
Chronic form, usually in women of childbearing age
Can be primary or secondary (e.g. to SLE)
ITP: first line Tx
Corticosteroids - good response in children, adults often relapse
ITP: refractory Tx
IVIG - splenic macrophages consume IVIG complexes instead of antibody:platelet complexes
Splenectomy
Thrombotic thrombocytopenic purpura (TTP): definition
Formation of pathologic microthrombi causes:
- consumption of platelets –> thrombocytopenia
- shearing of RBC’s –> microangiopathic hemolytic anemia
TTP: pathophysiology
ADAMTS13 normally cleaves vWF multimers into monomers for degradation
In TTP, decreased ADAMTS13 due to acquired autoantibody prevents vWF degradation –> abnormal platelet adhesion –> microthrombi
Microangiopathic hemolytic anemia: feature of which conditions?
1) Physical “chopper”: prosthetic heart valves, cardiac assist devices, disease heart valves (aortic stenosis)
2) Thrombosis “chopper”: TTP, HUS, DIC
Hemolytic uremic syndrome (HUS): presentation
Classic triad:
1) Microangiopathic hemolytic anemia
2) Uremia (microthrombi in kidneys –> acute renal failure)
3) Thrombocytopenia
HUS: causes
Shiga-toxin producing E. coli (STEC):
- E. coli O157:H7 (exposure to undercooked beef) toxin damages endothelial cells –> platelet microthrombi
TTP: presentation
Fatigue, weakness
Derm: petechiae, purpura (due to MAHA)
GI: bleeding, nausea, vomiting
CNS abnormalities
Minimal renal failure/injury despite renal involvement
[contrast with HUS]
MAHA: RBC on histology?
Schistocytes - RBC’s are getting sheared by microthrombi
TTP: Tx
Plasmaphoresis
Corticosteroids
HUS: Tx
Supportive care for symptoms
Bernard-Soulier syndrome: pathophysiology
Genetic GPIb deficiency causes impaired platelet adhesion
Bernard-Soulier syndrome: blood smear findings
Mild thrombocytopenia
Enlarged platelets
**
Mild thrombocytopenia: lack of GPIb - platelets don’t tend to live as long and tend to be destroyed
Enlarged platelets: more immature
Glanzmann thrombasthenia: pathophysiology
Genetic GpIIb/IIIa deficiency causes impaired platelet aggregation
Hemophilia A: presentation
Deep tissue, joint, postsurgical bleeding
Hemophilia A: pathophysiology
Factor VIII deficiency
Hemophilia A: FH
X-linked recessive OR de novo with no FH
Hemophilia A: labs
Increased PTT
Normal PT
Low Factor VIII
Normal platelet count
Hemophilia A: Tx
Recombinant Factor VIII
Hemophilia B: pathophysiology
Factor IX deficiency
Coagulation factor inhibitor: pathophysiology
Acquired antibody against a coagulation factor, most commonly VIII (8)
How to differentiate: hemophilia A vs coagulation factor inhibitor?
Presentation and labs similar
Need to do a MIXING TEST (patient’s plasma + normal plasma)
- if PTT corrects (due to normal factor in normal plasma) –> hemophilia A
- if PTT remains abnormal –> inhibitor present
von Willebrand’s Disease: pathophysiology
vWF deficiency –> impaired platelet adhesion
von Willebrand’s Disease: presentation
Mild mucosal and skin bleeding
Do not usually see deep tissue, joint, or postsurgical bleeding
von Willebrand’s Disease: labs
- Increased PTT b/c vWF helps to stabilize Factor VIII
- Abnormal ristocetin test (Normal: ristocetin causes vWF to bind to platelet GpIb –> aggregation. Abnormal: impaired aggregation)
von Willebrand’s Disease: treatment
Desmopressin (ADH analog)
Induces endothelial cells to release more vWF from Weibel-Palade bodies
Vitamin K deficiency: causes
1) Newborns - don’t yet have gut flora that normally produces Vit K (thus given Vit K injection at birth to prevent hemorrhagic disease of newborn)
2) Long-term antibiotic use - disrupts gut flora
3) Malabsorption - can lead to deficiency of fat-soluble vitamins (incl Vit K)
Heparin-induced thrombocytopenia: pathophysiology
IgG antibody against Heparin-Platelet Factor 4 complexes –> consumed by spleen –> thrombocytopenia
Fragments of destroyed platelets can activate other platelets and cause thrombosis
Heparin-induced thrombocytopenia: presentation
- New onset thrombocytopenia 5-10 days after initiation of heparin
- Venous/arterial thrombosis (presenting finding in 25% pts - but note not all thrombosis in pts on heparin represent HIT since these pts have higher baseline risk of thrombosis anyways)
- Necrotic skin lesions at heparin injection sites
Disseminated intravascular coagulation (DIC): definition
Pathologic activation of coagulation cascade involving:
- widespread microthrombi
- bleeding due to consumption of platelets, esp from IV sites and mucosal surfaces
DIC: name 5 associated causes
Secondary to:
- pregnancy: tissue factor in amniotic fluid enters maternal bloodstream
- sepsis (E. coli, N. meningitidis): endotoxins induce endothelial cells to produce tissue factor
- adenocarcinoma (mucin activates coagulation)
- APML - Auer rods composed of granules can enter bloodstream and activate coagulation
- rattlesnake bite venom
DIC: best screening test
Elevated D-dimer
- D-dimer = fragments of cross-linked fibrinogen
DIC: presentation
Bleeding (64%): petechiae, ecchymosis + directly from IV sites, mucosal surfaces
Acute renal failure (25%)
Hepatic, respiratory dysfunction
Shock
Disorders of fibrinolysis: pathophysiology (+name 2 causes)
Plasmin overactivity –> excessive cleavage of serum fibrinogen, e.g. due to:
- radical prostatectomy: release of urokinase activates plasmin
- liver cirrhosis: decreased a2-antiplasmin production
Disorders of fibrinolysis: presentation
Similar to DIC
Disorders of fibrinolysis vs DIC
Disorders of fibrinolysis:
- normal D-dimer b/c fibrin cross-links were never formed
- normal platelet count
- increased PT/PTT
DIC:
- increased D-dimer
- decreased platelet count due to consumption
- increased PT/PTT
Disorders of fibrinolysis: Tx
Aminocaproic acid - blocks activation of plasminogen
