Hematology Flashcards
Question
D. Iron sequestration in macrophages
Anemia of chronic disease
This patient with untreated systemic lupus erythematosus (SLE) has normocytic anemia with low serum iron and low total iron-binding capacity, raising strong suspicion for anemia of chronic disease (ACD). Most cases arise in those with chronic elevation of inflammatory cytokines due to underlying rheumatologic disease (eg, SLE), chronic infection, or malignancy. Although a number of inflammatory cytokines contribute to the development of ACD, the primary mediator is hepcidin, a small peptide released by the liver in response to inflammation.
Hepcidin binds to and inactivates iron channels (ferroportin) on enterocytes and reticuloendothelial macrophages, which results in reduced iron absorption in the gut and increased iron sequestration in the reticuloendothelial system. Because reticuloendothelial macrophages recycle senescent erythrocytes and provide >95% of daily iron for erythrocytosis, sequestration of iron in the reticuloendothelial system dramatically reduces serum iron concentration. This limits the amount of iron available for the generation of new erythrocytes and typically results in a normocytic (or slightly microcytic) anemia with a low reticulocyte response. In ACD, total iron-binding capacity is generally normal or slightly reduced due to cytokine-mediated suppression of transferrin.
(Choices A and E) Patients with SLE can develop immune-mediated hemolysis due to the generation of autoantibodies against the erythrocyte membrane; however, this typically results in extravascular hemolysis, which increases the intracellular enzyme lactate dehydrogenase. The presence of normal lactate dehydrogenase in this case makes hemolysis less likely. Patients with SLE also sometimes develop gastrointestinal bleeding from serositis (or chronic NSAID use), which can lead to iron deficiency anemia. However, iron deficiency anemia is typically associated with microcytic anemia and a high total iron-binding capacity (because transferrin levels are markedly increased).
(Choices B and C) Conditions associated with rapid cell turnover can result in folate deficiency due to increased folate use during the generation of new cells. Intrinsic factor antibodies are a common cause of vitamin B12 deficiency. However, folate and vitamin B12 deficiency are generally marked by macrocytic anemia with a normal or high serum iron level.
Educational objective:
Anemia of chronic disease is a consequence of chronically elevated inflammatory cytokines, most importantly hepcidin. This peptide inactivates iron channels on enterocytes and reticuloendothelial macrophages, leading to reduced iron absorption and reduced iron release from the reticuloendothelial system. The net result is normocytic or slightly microcytic anemia with low reticulocyte response, low serum iron level, and normal or low total iron-binding capacity.
Glanzmann thrombasthenia Pathophysiology
an autosomal recessive disorder that is caused by a deficient or defective glycoprotein (GP) IIb/IIIa on platelet surfaces and that typically presents in childhood with mucocutaneous bleeding. Peripheral smear shows no platelet clumping (an important clue for diagnosis).
Platelets are responsible for formation of platelet plugs that stop bleeding from injured vessels (primary hemostasis). Vessel wall injury exposes the subendothelial collagen and matrix. Platelet attachment to exposed collagen is strengthened by GP Ib binding to von Willebrand factor on the vessel wall. The resulting platelet activation leads to the following:
Release of mediators (eg, ADP, thromboxane A2 [TXA2]) into circulation, which in turn activates other platelets
Conformational structural change of GP IIb/IIIa on platelet surfaces; this allows thousands of copies of GP IIb/IIIa to bind fibrinogen, thereby forming a platelet plug.
Abciximab, a GP IIb/IIIa receptor antagonist, inhibits binding of this receptor to fibrinogen. Abciximab and other GP IIb/IIIa inhibitors are useful for treatment of unstable angina and acute coronary syndrome, particularly in patients undergoing percutaneous coronary intervention.
Abundant intravascular fibrin deposition (ie, fibrin thrombi) in the absence of vascular inflammation
DIC
Disseminated intravascular coagulation is characterized by abundant intravascular fibrin deposition (ie, fibrin thrombi) in the absence of vascular inflammation. It occurs most often in the setting of trauma, sepsis, or malignancy and presents with bleeding (eg, purpura) due to thrombocytopenia and coagulopathy.
Obliterative endarteritis with lymphocytes and plasma cells is seen with
later-stage syphilis, which can cause arthralgias, renal abnormalities, and a rash; classic skin findings include scaly red/brown macules or papules that are typically diffuse and involve the palms and soles.
Perivascular necrotizing granulomas with eosinophilic infiltration are characteristic of
eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), a small- to medium-vessel vasculitis. It can cause renal, skin, and joint involvement later in life (eg, third to fourth decades) but initially presents with asthma symptoms, which are not seen in this patient.
Churg-Strauss syndrome)
eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), a small- to medium-vessel vasculitis. It can cause renal, skin, and joint involvement later in life (eg, third to fourth decades) but initially presents with asthma symptoms, which are not seen in this patient.
Transmural granulomatous inflammation with fragmentation of elastic fibers is a typical finding of
giant cell arteritis, seen in adults age >50. It involves medium/large arteries and most commonly presents with headache.
