What substances accumulate in acute intermittent porphyria?
Porphobilinogen, δ-ALA, and uroporphyrin (in the urine)
What treatment is available for patients with acute intermittent porphyria?
Glucose or heme, both of which inhibit ALA synthase to decrease buildup of heme precursors
A patient presents with blisters upon exposure to sunlight and you suspect a porphyria; what is the most likely cause?
Porphyria cutanea tarda, the most common porphyria
In porphyria cutanea tarda, there is a defect in the enzyme _____, resulting in an accumulation of _____.
Uroporphyrinogen decarboxylase; uroporphyrin, causing tea-colored urine
What enzyme is affected in patients with X-linked sideroblastic anemia?
δ-ALA synthase, which is responsible for the rate-limiting step of heme synthesis; conversion of glycine and succinyl-Co-A to aminolevulinic acid
What cofactor is necessary for the rate-limiting step in heme synthesis?
Vitamin B6, which is needed to convert glycine and succinyl-Co-A to aminolevulinic acid
Which step in heme synthesis requires iron?
The final step, where protoporphyrin is converted to heme by ferrochelatase
How does heme provide negative feedback for its own synthesis?
Heme inhibits ALA dehydratase, the second step in heme synthesis
What condition should be suspected in a patient who has bluish lines on his gums and thick white lines on long bone epiphyses on x-ray?
Lead poisoning; the blue lines around teeth are Burton's lines, and the white lines near the epiphysis are lead lines
Name two hematologic manifestations of lead poisoning.
Basophilic stippling on erythrocytes and sideroblastic anemia
Name three neurologic manifestations of lead poisoning.
Encephalopathy, abdominal pain, and wrist and foot drop
What are the main treatments for lead poisoning in adults?
Chelation therapy; dimercaprol or EDTA are first-line treatments
What treatment is indicated in a child who has lead poisoning?
Succimer (remember: it sucks to be a kid who eats lead)
What coagulation test will indicate there is a problem with platelet function?
Bleeding time will be increased; there will be no change in prothrombin time or partial thromboplastin time
A patient has bleeding from the gums, epistaxis, petechiae, and purpura; what is the likely defect in coagulation?
These describe the microhemorrhages associated with a platelet disorder; there may or may not be a decreased number of platelets
Which platelet disorder has an increased bleeding time but normal platelet count?
Glanzmann's thrombasthenia; all have an increased bleeding time, whereas Bernard-Soulier disease, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura have decreased platelet counts
Bernard-Soulier disease causes a defect in the platelet's interaction with what molecule?
Endothelial collagen; there is a decrease in the molecule glycoprotein Ib for platelet-to-collagen adhesion
Glanzmann's thrombasthenia causes a defect in what platelet interaction?
Poor platelet-to-platelet aggregation in the platelet plug due to decreased glycoprotein IIb/IIIa
What is the antibody target in immune thrombocytopenic purpura?
Immune thrombocytopenic purpura is caused by antibodies to glycoprotein IIb/IIIa causing platelet destruction
What enzyme is deficient in patients with thrombotic thrombocytopenic purpura?
ADAMTS-13, a metalloproteinase that degrades von Willebrand's multimers
What is the role that von Willebrand's multimers play in the development of thrombotic thrombocytopenic purpura?
The large von Willebrand's multimers cause increased platelet aggregation (bind glycoprotein Ib) and thrombosis
A patient develops renal failure, confusion, thrombocytopenia, fever, and schistocytes on peripheral smear; what is the diagnosis?
This is the classic pentad of thrombotic thrombocytopenic purpura
What coagulation factors are evaluated when you order a prothrombin time test?
Factors I, II, V, VII, and X; the extrinsic pathway
What coagulation factors are evaluated when you order a partial thromboplastin time test?
All coagulation factors except VII and XIII; the intrinsic pathway
Hemophilia A is caused by a deficiency of _____, whereas hemophilia B (Christmas disease) is caused by a deficiency of _____.
Factor VIII; factor IX
What are the prothrombin time and partial thromboplastin time results in a patient with hemophilia (A or B)?
The prothrombin time will be normal and the partial thromboplastin time will be elevated because hemophilia affects the intrinsic pathway
A patient presents to the emergency room with a large swollen joint tapped and found to be full of blood. He has a history of easy bruising. What condition should you consider in your diagnosis?
Spontaneous hemarthrosis, which is a macrohemorrhage seen in hemophilia (compared to petechiae or purpura in platelet disorders)
What are the prothrombin time and partial thromboplastin time changes in a patient with vitamin K deficiency?
Vitamin K deficiency causes both prothrombin time and partial thromboplastin time elevations
What are the platelet count, bleeding time, prothrombin time, and partial thromboplastin time in a patient with von Willebrand's disease?
There is an elevated bleeding time due to a defect in platelet adhesion; in severe von Willebrand's deficiency, there is also an increase in partial thromboplastin time due to decreased half-life of factor VIII
Why can you see an elevated partial thromboplastin time in a patient with von Willebrand's disease?
von Willebrand's factor carries and protects factor VIII; deficiencies in von Willebrand's factor can cause intrinsic pathway coagulopathies related to factor VIII deficiency