Heme Review Flashcards
Which coagulation factor is deficient in hemophilia A? What’s the inheritance pattern?
factor VIII; X-linked recessive
Which coagulation factor is deficiency in hemophilia B? What is the inheritance pattern?
factor IX; X-linked recessive
What is the clinical consequence of a deficiency in either protein C or protein S?
increased coagulation
What factors are part of the intrinsic pathway?
8,9,11,12
What factors are part of the extrinsic pathway?
7
What factors are part of the common pathway?
1,2,5,10,13
What factors does the PT measure?
1,2,7,10 (extrinsic and common)
What factors does the PTT measure?
everything except 7 and 13 (intrinsic and common)
What lab test is used to monitor adequate anticoagulation in a patient taking heparin? Warfarin?
heparin - monitor PTT
warfarin - monitor PT and INR
What is the treatment for an overdose of heparin? Warfarin?
heparin - protamine sulfate
warfarin - Vit K, FFP, PCC (the last two only if active bleeding)
What is the treatment for heparin-induced thrombocytopenia?
stop heparin, switch to a direct thrombin inhibitor
What is the presentation of erythroblastosis fetalis?
Clinical features in neonate:
- anemia due to hemolysis of RBCs by maternal antibodies
- jaundice -> possible kernicterus
- hydrops fetalis (generalized fetal edema)
- intrauterine death
What allows RBCs to change shape as they pass through vessels?
biconcave shape (anucleate) d/t spectrin
Which pathologic form of RBC would you see with lead poisoning?
basophilic stippling
Which pathologic form of RBC would you see with G6PD deficiency?
Heinz bodies, bite cells
Which pathologic form of RBC would you see with DIC?
schistocytes
Which pathologic form of RBC would you see with abetalipoproteinemia?
acathocytes (spur cells)
Which pathologic form of RBC would you see with asplenia?
Howell-Jolly bodies, target cells
Where does fetal erythropoiesis take place? In which adult bones does erythropoiesis take place?
Fetal - yolk sac, liver, spleen, BM
Adult - axial skeleton (sternum, ribs, pelvis, vertebrae)
What are some of the different causes of polycythemia?
decreased plasma volume (dehydration, burns)
decreased O2 - pulmonary problems, heart Dz, high altitude
increased EPO - ectopic tumors (PRHH - pheochromocytoma, renal cell carcinoma, hemangioblastoma, hepatocellular carcinoma)
polycythemia vera
What are the hematologic and non-hematologic findings in a patient with lead poisoning?
hematologic - basophilic stippling, microcytic anemia
non-hematologic - encephalopathy, memory loss, HA, wrist/foot drop, lead lines on gingival, lead lines on bones (kids), abdominal colic, renal failure
What is the rate-limiting step of heme synthesis? What is required for the reaction?
delta-ALA synthase, Vit B6
What inhibits delta-ALA synthase?
glucose and heme
What enzyme deficiency causes acute intermittent porphyria?
uroporphyrinogen-1-synthase
What enzyme deficiency causes porphyria cutanea tardy?
uroporphyrinogen decarboxylase
What enzyme deficiencies can cause lead poisoning?
delta-ALA-dehydratase and ferrochelatase
What is the serum iron, TIBC, ferritin, and % transferring saturation (decreased or increased) for iron deficiency anemia?
serum iron - decreased
TIBC - increased
ferritin - decreased
% transferrin saturation - decreased (<12%)
What is the serum iron, TIBC, ferritin, and % transferring saturation (decreased or increased) for anemia of chronic disease?
serum iron - decreased
TIBC - decreased
Ferritin - normal or increased
% transferrin saturation - normal (>18%)
What is the serum iron, TIBC, ferritin, and % transferring saturation (decreased or increased) for hemochromatosis?
serum iron - increased
TIBC - decreased
ferritin - increased
% transferrin saturation - increased
What is the serum iron, TIBC, ferritin, and % transferring saturation (decreased or increased) for sideroblastic anemia?
serum iron - increased
TIBC - decreased
ferritin - increased
% transferrin saturation - normal or increased
What test can be used to diagnose beta thalassemia minor?
hemoglobin electrophoresis to look for greater than normal HgA2
What should you rule out in a man over 50 with new onset iron deficiency anemia?
colon cancer
Causes of hypo chromic, microcytic anemia
iron deficiency anemia alpha-thalassemia beta-thalassemia anemia of chronic Dz lead poisoning
Skull x-ray shows a “hair-on-end” appearance
marrow hyperplasia -> beta thalassemia or sickle cell Dz
What are the causes of aplastic anemia?
radiation/drugs -> chloramphenicol and cancer drugs
viruses
fanconi syndrome
idiopathic
A patient is diagnosed with a microcytic, megaloblastic anemia. What is the danger of giving folate alone?
will not treat a potential Vit B12 deficiency, but it will mask the anemia
microcytic anemia and swallowing difficulty and glossitis
Plummer-Vinson syndrome
Microcytic anemia with >3.5% HgA2
beta thalassemia minor
macrocytic anemia and hypersegmented neutrophils
folate/B12 def -> megaloblastic anemia
megaloblastic anemia not correctable by B12 or folate supplements
oratic aciduria
microcytic anemia and basophilic stippling
lead toxicity
microcytic anemia reversible with B6 supplements
sideroblastic anemia
HIV-positive patient with macrocytic anemia
Zidovudine
normocytic anemia and elevated creatinine
chronic kidney disease
Acute intermittent porphyria
autosomal dominant
porphobilinogen deaminase deficiency (AIA uroporphyrinogen I synthase)
Sx - 5P’s - painful abdomen, port wine-colored urine, polyneuropathy, psychological disturbances, precipitated by drugs (barbiturates, seizure drugs, rifampin, metoclopramide)
Tx 0 glucose and heme, which inhibit ALA synthase
Porphyria cutanea tarda
autosomal dominant
uroporphyrinogen decarboxylase deficiency
Sx - tea-colored urine (uroporphryin build up), blistering cutaneous photosensitivity and hyperpigmentation, hypertrichosis, increased liver function tests; exacerbated by alcohol consumption, and is associated with HepC
sideroblastic anemia
causes: genetic, alcohol is most common reversible acquired cause, also Vit B6 deficiency, copper deficiency, and isoniazid
Lab findings: increased iron, increased ferritin, ringed sideroblasts (with iron-laden, Prussian blue-stained mitochondria) seen in BM
Tx - B6
alpha-thalassemia
defect: alpha globin gene deletions -> decreased alpha-globin synthesis
prevalent in Asian and African populations
4 allele deletion: Hb Barts, incompatible with life, hydrops fetalis (gamma4 Hgb)
3 allele deletion: HbH disease; very little alpha-globin; beta4
2 allele deletion: less clinically severe anemia
1 allele deletion: no anemia
beta-thalassemia
decreased beta globin synthesis; prevalent in mediterranean populations
beta-thalassemia minor - beta chain is underproduced; usually asymptomatic, diagnosis is confirmed by increased HbA2 on electrophoresis
beta-thalassemia major - beta chain absent -> severe microcytic, hypo chromic anemia with target cells and increased anisopoikilocytosis requiring blood transfusion (secondary hemochromatosis)
crew cut on skull x-ray, chipmunk facies; extra medullary hematopoiesis -> hepatosplenomegaly
increased risk of parvoB19-induced aplastic crisis
increased HbF
How do you treat secondary hemochromatosis d/t transfusions in beta-thalassemia major?
deferoxamine (iron chelator)
What drugs cause increased oxidative stress in patient with G6PD deficiency?
Spleen Purges Nasty Inclusions From Damaged Cells S - sulfonamides P - primaquine N - nitrofurantoin I - isoniazid F - fava beans D - dapsone C - chloroquine
