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Citrate-mediated chelation of a cation
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Decreased levels of a fat-soluble vitamin
Decreased levels of serum albumin
Increased sequestration by serum phosphate
Surgery-induced decrease in parathyroid hormone
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This patient presents with abdominal ecchymoses, involuntary guarding, and hemodynamic instability (hypotension, tachycardia) in the setting of trauma, which are indicative of intra-abdominal hemorrhage. After receiving blood transfusion products, he develops tetany (involuntary muscle spasms), which is most likely due to hypocalcemia caused by chelation of calcium by the citrate found in blood products. Normally, most serum calcium exists either in ionized form, which is biologically active, or bound to albumin. A small fraction is complexed with various inorganic anions, such as phosphate and citrate. Homeostatic calcium regulation is performed by the parathyroid gland, which releases parathyroid hormone (PTH) in response to ionized calcium sensors. However, massive blood transfusions are also known to shift this balance due to chelation of ionized calcium by the citrate found in blood products. This results in hypocalcemia, which presents with tetany, paresthesias, and muscle cramps. This can be prevented by blood infusion at a slower rate to allow for hepatic metabolism of citrate. If ionized hypocalcemia develops, it can be corrected with either calcium chloride or calcium gluconate. Giancarelli et al. studied patients receiving massive transfusions in the trauma setting and measured the incidence of hypocalcemia. They found that 97% of these patients developed hypocalcemia and 71% developed severe hypocalcemia. Incorrect Answers: Answer 2: Decreased levels of a fat-soluble vitamin describes hypocalcemia secondary to vitamin D deficiency. Vitamin D deficiency-induced hypocalcemia causes a compensatory increase in PTH secretion, which also results in hypophosphatemia. However, the temporal correlation of this patient’s symptoms with massive blood transfusion makes citrate chelation more likely. Answer 3: Decreased levels of serum albumin describes a variety of disorders characterized by poor nutrition or protein loss, including chronic liver disease and malignancy. This results in decreased serum total calcium due to less protein-bound calcium, but does not affect the ionized calcium concentration. Ionized calcium is physiologically active and is what the calcium-sensing receptors in the parathyroid gland respond to. Thus, this is less likely to be symptomatic. Answer 4: Increased sequestration by serum phosphate describes states of hyperphosphatemia such as tumor lysis syndrome, in which massive amounts of phosphate complex with calcium, resulting in calcium phosphate precipitates and hypocalcemia. There is no evidence that this young patient has an underlying malignancy. Answer 5: Surgery-induced decrease in parathyroid hormone commonly occurs after thyroidectomy, in which the parathyroid glands are inadvertently damaged. Reduced PTH secretion results in hypocalcemia. However, this patient is receiving an exploratory laparotomy, not a thyroid procedure. Bullet Summary: Massive blood transfusion can cause hypocalcemia due to chelation of ionized calcium by citrate molecules present in blood products.
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