A 74-year-old woman is brought to the hospital by her daughter due to unusual bruising for the past two days and a persistent nosebleed that has lasted for over an hour. The patient was recently hospitalized for a severe skin and soft tissue infection, during which she received a 14-day course of broad-spectrum intravenous antibiotics. She has also had poor oral intake over the last three weeks due to decreased appetite. Physical examination reveals multiple large ecchymoses on her forearms and thighs, as well as petechiae on her oral mucosa.
Laboratory studies show the following:
Hemoglobin: 11.8 g/dL
Platelet count: 220,000/μL
Prothrombin time (PT): 28 seconds (Normal: 11–13.5s)
Partial thromboplastin time (PTT): 52 seconds (Normal: 25–35s)
Bleeding time: Normal
Which of the following is the most likely mechanism of this patient's coagulopathy?
The correct answer is:
B) Failure of gamma-carboxylation of specific glutamic acid residues
This patient is presenting with vitamin K deficiency, likely caused by a combination of poor dietary intake and the recent use of broad-spectrum antibiotics, which depleted the vitamin K-producing bacterial flora in her gut. Vitamin K is a necessary cofactor for the enzyme gamma-glutamyl carboxylase. This enzyme adds a carboxyl group to glutamic acid residues on Factors II, VII, IX, and X, as well as Proteins C and S. This chemical modification allows these factors to bind calcium and adhere to phospholipid membranes, a crucial step in the coagulation cascade. Without functional vitamin K, these factors are synthesized but remain inactive. Because vitamin K-dependent factors are found in the extrinsic (VII), intrinsic (IX), and common (II, X) pathways, both the PT and PTT are prolonged, though the PT typically rises first due to the short half-life of Factor VII.
Answer choice A: Autoimmune destruction of clotting factors, is incorrect. This refers to acquired factor inhibitors like a Factor VIII inhibitor. While this would prolong the PTT, it would not typically affect the PT unless an inhibitor against a common pathway factor were present, which is significantly rarer than vitamin K deficiency in this clinical context.
Answer choice C: Impaired synthesis due to liver failure, is incorrect. While liver failure also causes a prolonged PT and PTT, this patient’s history of recent antibiotic use and poor intake strongly points to a nutritional/microbiome-related deficiency rather than primary hepatocyte failure.
Answer choice D: Inhibition of the ADAMTS13 protease, is incorrect. This describes the mechanism of thrombotic thrombycytopenic purpurua (TTP). TTP presents with thrombocytopenia and schistocytes, but the coagulation studies (PT and PTT) remain normal. Antibiotics do not typically cause TTP.
Answer choice E: Selective depletion of contact activation factors, is incorrect. The contact activation pathway (Factor XII, prekallikrein, high-molecular-weight kininogen) affects the PTT only. Deficiencies in these factors generally do not cause clinical bleeding.
Key Learning Point
Vitamin K deficiency results in the under-carboxylation of Factors II, VII, IX, and X. It is commonly seen in patients with malabsorption, biliary obstruction, or those on long-term broad-spectrum antibiotics. The laboratory hallmark is a prolonged PT and PTT with a normal platelet count. It can be rapidly reversed with vitamin K administration (phytonadione).
