Hemophilia & Bleeding Disorders Flashcards
hemophilia - overview
*can be congenital or acquired
*inability to from adequate complete clots due to specific clotting factor deficiency:
-mechanism: impaired/dysfunctional thrombin burst
*most commonly an X-linked recessive disorder, so affects males predominantly (females are often symptomatic carriers)
types of hemophilia
*factor VIII deficiency = classic hemophilia = hemophilia A
*factor IX deficiency = Christmas disease = hemophilia B
*factor XI deficiency (occasionally called hemophilia C)
coagulation mnemonics
*the PT (extrinsic) and the PTT (intrinsic) pathways meet at factor X because “X” marks the spot
*factor V is a cofactor for factor X, and you can remember this because V fits into the notch of X
*factor Xa converts prothrombin into thrombin
*thrombin converts the soluble molecule fibrinogen into a fibrin clot
what clotting factor should we investigate if ONLY the PT is prolonged
factor VII deficiency
what clotting factor should we investigate if ONLY the PTT is prolonged
deficiencies of factors 12, 11, 9, or 8 (XII, XI, IX, or VIII)
what clotting factor should we investigate if BOTH the PT and PTT are prolonged
most likely, factor X deficiency
clotting factor deficiencies that are clinically significant
*deficiencies of factors XI, IX, VIII, VII, X, V, prothrombin, and fibrinogen are clinically significant
*inhibitors of these factors are clinically significant for bleeding
note - deficiency of factor XII, and the presence of the lupus anticoagulant, are not clinically significant
hemophilia inheritance pattern
*X-linked recessive
*affects males predominantly (can occur in females though)
*can skip generations
*30% spontaneous (de novo) mutations
hemophilia - genetics
*factor VIII (hemophilia A) and factor IX (hemophilia B) genes are located near the top of the long arm of the X chromosome
*point mutations are the most common, but different mutation known to have different clinical phenotypes
*result in either case is absence of or low level of FVIII or FIX activity
hemophilia - female carriers
*majority of symptomatic individuals are male
*heterozygote females can be “symptomatic carriers” with bleeding tendencies and pattern most centered around baseline levels
*lyonization effect or double heterozygote inheritance can result in lower residual activity and clinically relevant bleeding
hemophilia - clinical manifestations
*joint bleeds -> target joints (most relevant)
*deep muscle bleeds
*hematomas
*post-surgery/post-trauma
*dental extractions
*intracranial hemorrhage
hemophilia - severity of disease
<1% clotting activity = severe; sx in early childhood & spontaneous bleeds
1-5% clotting activity = moderate; bleeding after minor trauma or surgery; may be spontaneous
5-30% clotting activity = mild; only bleed after trauma or surgery
hemophilic arthropathy
*recurrent bleeds in joints
-inflammation, bony destruction, acute pain
-chronic pain (arthritis)
*decreased range of motion
*long-term disability, psychosocial consequences
development of hemophilic arthropathy
repeated joint bleeds → hemophilic arthropathy → pain and functional impairment
*proliferation of capillaries; synovial cell hyperplasia
*inflammatory cells infiltrate joint space → destruction of cartilage → synovial proliferation into joint space, burrowing into bone and covering cartilage → destruction of joint!
hemophilia - intramuscular/soft tissue bleeding
areas of greatest concern:
*face, neck, mouth, eye
*palm of hand, wrist
*calf
*thigh or groin
*hip or shoulder
*hematuria, GI tract bleeding
note - bleeding of muscles or soft tissues occur less frequently than joint bleeds
