Porphyrias, Hemostasis Disorders Flashcards
Lead Poisoning
Ferrochetalase and ALAD
^ protoporphyrin, ALA
Microcytic anemia w basophilic stippling
GI and Kidney disease
Kids - lead paint –> mental deterioration
Adults - environment –> headache, memory loss, demyelination
Acute Intermittent Porphyria
Porphobilinogen deaminase
^ porphobilinogen, ALA, coporphobilinogen in urine
Painful abdomen, Purple urine, Polyneuropathy, Psych disturbances, Precipitated by drugs (CYP450 inducers, alcohol), Palpitations.
Tx: glucose and hemin/heme (inhibit ALA synthase).
Porphyria Cutanea Tarda
Uroporphyrinogen decarboxylase
^uroporphyrin (tea-colored urine)
Blistering cutaneous sensitivity.
Most common.
Hemophilia
-PT, ^PTT
Intrinsic pathway defect.
A: factor 8 deficient, X-recessive.
B: factor 9 deficient, X-recessive.
C: factor 11 deficient, autosomal recessive.
Macrohemorrhage: hemarthroses, easy bruising, bleeding after surgery.
Tx: desmopressin, deficient factor.
Vitamin K Deficiency
^PT, ^PTT
Normal bleeding time.
General coagulation defect.
v activity of factors 2, 7, 9, 10, proteins C and S.
Bernard-Soulier Syndrome
-/v PC (platelet count)
^ BT (bleeding time)
Defect in platelet plug formation.
Large platelets.
v GpIb –> defect in platelet-vWF adhesion.
Glansmann Thrombasthenia
-PC
^BT
Defect in platelet plug formation.
v GpIIb/IIIa –> defect in platelet-platelet aggregation.
Labs: blood smear shows no platelet clumping.
Hemolytic-Uremic syndrome
vPC
^BT
Thrombocytopenia, microangiopathic hemolytic anemia, acute renal failure.
Kids w diarrhea, commonly caused by Shiga toxin from E.coli.
Adults don’t have diarrhea or require the infection.
Similar to TTP.
Immune Thrombocytopenia
vPC
^BT
Anti-GpIIb/IIIa antibodies –> splenic macrophage consumption of platelet-antibody complexes.
Viral illness.
^ megakaryocytes on bone marrow biopsy.
Tx: steroids, IVIG, splenectomy
Thrombotic Thrombocytopenic Purpura (TTP)
vPC
^BT
Inhibition or deficiency of ADAMTS (vWF metalloprotease) –> v degradation of vWF.
^ large vWF multimers –> ^ platelet adhesion –> ^ platelet aggregation and thrombosis.
Schistocytes, ^ LDH.
Neuro and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia.
Tx: plasmapheresis, steroids.
von Willebrand Disease
-PC, ^BT, -PT, ^PTT.
vWF carries/protects factor 8.
Intrinsic pathway defect: v vWF –> ^ PTT.
Defect in platelet plug formation: v vWF –> defect in platelet-vWF adhesion.
Autosomal dominant. Mild, but common.
No platelet aggregation w ristocetin.
Tx: desmopressin (releases vWF stored in endothelium).
Disseminated Intravascular Coagulation (DIC)
vPC, ^BT, ^PT, ^PTT.
Widespread activation of clotting –> deficiency in clotting factors –> bleeding state.
Causes: Sepsis (gm-), Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome Transfusion.
(STOP Making New Thrombi)
Schistocytes, ^ fibrin degradation products (D-dimer), v fibrinogen, v factors 5 and 8.
Antithrombin Deficiency
Inherited.
No direct effect on PT, PTT, or thrombin time.
Diminishes the increase in PTT following heparin admin.
Can be acquired: renal failure/nephrotic syndrome –> antithrombin loss in urine –> v inhibition of factors 2 and 10.
Factor V Leiden
Production of mutant factor 5 (G–>A DNA point mutation) –> Arg506Gln mutation near the cleavage site).
Resistant to degradation by protein C.
Most common for Caucasians.
Complications: DVT, cerebral vein thromboses, recurrent pregnancy loss.
Protein C or S deficiency
v ability to inactivate factors 5 and 8.
^ risk of thrombotic skin necrosis w hemorrhage after admin of warfarin.
protein C Cancels and protein S Stops coagulation
