Bleeding Disorders Flashcards
Normal hemostasis requires a balance between what 3 elements?
Platelets, coagulation factors, and endothelial cells
Senile purpura, purpura simplex, and scurvy are all hemostatic dysfunctions that occur in what compartment of the body?
Extravascular compartment
What event causes the vessel wall weakness and purpura of amyloidosis, cyroglobulinemia, other paraproteinemias, and arteritis?
Immunoglobulin fragment deposition
What platelet disease, also known as Rendu-Osler-Weber Syndrome, is characterized by dilation and thinning of venule and capillary walls, arteriovenous malformations of multiple solid organs, and telangiectasias of the mucous membranes and dermis?
Hereditary hemorrhagic telangiectasia
What platelet disease, also known as allergic purpura, is characterized by IgA and complement mediated vascular damage, platelet plugs, and leukocytoclastic vasculitis?
Henoch Schonlein purpura
How does the presentation of Henoch Schonlein purpura differ between kids and adults?
In kids: follows viral infections, self-limited
In adults: often from drug exposure, chronic
What term describes an inflammation of blood vessels that destroys WBCs?
Leukocytoclastic vasculitis
The congenital thrombocytopenias or MYH9-related platelets disorders (May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome and Sebastian platelet syndrome) are due to what cause of thrombocytopenia?
Decreased platelet production
What kind of thrombocytopenia is an autoimmune disease due to antibodies directed against platelet or megakaryocyte antigens?
ITP (idiopathic thrombocytopenic purpura)
HIT (heparin-induced thrombocytopenia) type I and II belong to what category of thrombocytopenia? Which type is immune mediated, and which type is more dangerous?
Drug-induced thrombocytopenia; type II is autoimmune and more dangerous
Which type of HIT involves IgG antibodies against platelet factor 4–heparin complexes, leading to a hypercoagulable state?
HIT type II
List 2 conditions that can follow the increased platelet destruction of pregnancy-associated thrombocytopenia.
Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets)
GIve 3 kinds of neonatal thrombocytopenias associated with increased platelet destruction.
X-linked (ex. Wiskott-Aldrich syndrome), Fanconi anemia, NAIT (neonatal alloimmune thrombocytopenia)
Posttransfusion purpura involves platelet destruction because of antibodies against what platelet antigen?
HPA-1
List the 5 features that unite the thrombotic microangiopathies.
Thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, fever, and renal impairment
The pathology of what 2 disorders result from widespread platelet aggregation and hyaline thrombi deposition in the microcirculation?
TTP (thrombotic thrombocytopenic purpura) and HUS (hemolytic uremic syndrome) - the thrombotic microangiopathies
The pathogenesis of TTP is believed to involve a deficiency in what metalloprotease that normally cleaves von Willebrand factor?
ADAMTS13
What hemostatic disorder of platelets features PAS (periodic acid-Schiff) positive microthrombi and no inflammation in the microvasculature?
TTP (thrombotic thrombocytopenic purpura)
While TTP can be seen in all ages and has a variety of causes, HUS is generally seen in what age group and caused by what 2 infectious diseases?
Children; follows E. coli or Shigella infection
Comparing TTP vs. HUS: In which one is platelet aggregation due to lack of ADAMTS13 metalloprotease and large vWF multimers, and in which one is it due to endothelium damage?
TTP; HUS
Contrast the 4 causes of reactive thrombocytosis and the 1 main cause of clonal thrombocytosis.
Reactive can be due to iron-deficiency anemia, splenectomy, cancer, or chronic inflammation.
Clonal is due to myeloproliferative neoplasms.
What coagulation factors are mutated in hemophilia A and B?
VIII; IX
Which coagulopathy is the most common X-linked inherited bleeding disorder, seen in every 5,000-10,000 males?
Hemophilia A
Of the 3 types of von Willebrand disease, which involves qualitative defects, which involves quantitiative defects, and which involves complete absence of vWF?
Type I is quantitative deficiency (all multimers decreased)
Type II is qualitative deficiency (IIa, missing high MW multimers; IIb, increased platelet affinity)
Type III is no vWF activity (and often low factor VIII, too)
Which type of von WIllebrand disease is the rarest and most severe?
Type III (complete absence of vWF activity and only 10% of normal factor VIII)
Liver disease or malabsorption due to antibiotics can lead to a deficiency in what vitamin, which is needed to make factors II, V, VII, IX, and X and to carboxylate their Glu residues? Which factor does not need carboxylation in order to be active?
Vitamin K; factor V
List 3 stages in disseminated intravascular coagulation.
- Uncontrolled thrombin generation forms fibrin clots in the microvasculature
- Fibrinolysis consumes platelets and coagulation factors
- Hemorrhagic diathesis (tendency to bleed) results
What molecule is the main trigger of DIC because it initiates thrombin formation/activation?
Tissue factor
How does microangiopathic hemolytic anemia occur in DIC?
Webs of intravascular fibrin degrade RBCs
What is the most common genetic disorder associated with hypercoagulability? What enzyme does the body become resistant to?
Factor V Leiden mutation; Activated protein C resistance
What hypercoagulability disorder features thrombosis of arteries and veins, spontaneous abortions, and IgG mediated thrombocytopenia and anemia?
Antiphospholipid antibody syndrome
Describe the effect of lupus anticoagulant antiphospholipid antibodies on blood clotting in vitro and in vivo.
In vitro - prolongs PTT, but in vivo - causes hypercoagulation
