A 50-year-old woman with a history of systemic lupus erythematosus is admitted with fever, chills, vomiting, and burning pain when urinating. Temperature is 39.3 C (102.7 F), blood pressure is 80/50 mm Hg, pulse is 120/min, and respirations are 20/min. On examination, costovertebral angle tenderness is present. The patient is given intravenous antibiotics. Over the next several hours, she has decreased urine output despite aggressive intravenous hydration. Blood is oozing around the central venous catheter. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 9.0 g/dL |
| Platelets | 68,000/mm3 |
| Leukocytes | 24,500/mm3 |
| Coagulation studies | |
| Prothrombin time | 23 sec |
| Partial thromboplastin time | 60 sec |
| Plasma fibrinogen | 100 mg/dL (150-350) |
Which of the following is the most likely cause of this patient's hematologic abnormalities?
Laboratory characteristics of coagulopathies | |||||
Platelet count | Prothrombin time | Partial thromboplastin time | Plasma fibrinogen values | Peripheral blood smear | |
von Willebrand disease | Normal | Normal | ↑ | Normal | Normal |
Immune thrombocytopenic purpura | ↓ | Normal | Normal | Normal | Isolated thrombocytopenia |
TTP-HUS | ↓ | Normal | Normal | Normal | RBC fragmentation |
Disseminated intravascular coagulation | ↓ | ↑ | ↑ | ↓ | RBC fragmentation |
| HUS = hemolytic uremic syndrome; RBC = red blood cell; TTP = thrombotic thrombocytopenic purpura. | |||||
This patient's costovertebral angle tenderness, dysuria, and leukocytosis are indicative of acute pyelonephritis complicated by septic shock (hypotension, tachycardia). Her laboratory results show a consumptive coagulopathy (thrombocytopenia, prolonged PT/PTT, low fibrinogen), which, along with bleeding from the central catheter site, are likely due to disseminated intravascular coagulation (DIC).
DIC is a common complication of sepsis (particularly with gram-negative organisms) because lipopolysaccharide is a procoagulant that triggers the coagulation cascade. This leads to the formation of fibrin- and platelet-rich thrombi in the vasculature, which consumes platelets (thrombocytopenia), coagulation factors (prolonged PT/PTT), and fibrinogen. Fibrinolysis is then triggered to degrade the clots, which elevates D-dimer (a fibrin degradation product) and depletes protein C, protein S, and antithrombin. The thrombi also often shear red blood cells, leading to microangiopathic hemolytic anemia (MAHA).
Most patients with acute DIC have signs of bleeding, such as oozing from vascular catheters, mucocutaneous bleeding, ecchymosis, or petechiae. End organ damage (eg, renal insufficiency, pulmonary hemorrhage) is also common.
(Choice A) Anticardiolipin antibody is antiphospholipid antibody often seen in patients with lupus erythematosus. It can cause antiphospholipid antibody syndrome, which is marked by thromboembolism and fetal loss (not bleeding). Although patients often have prolonged PTT (because the antiphospholipid interferes with the PTT test), PT is normal.
(Choice B) Thrombotic thrombocytopenic purpura (TTP) is caused by reduced activity of von Willebrand factor–cleaving protein ADAMTS13, leading to the accumulation of ultra-large von Willebrand factor multimers that trap platelets and generate platelet-rich thrombi in the microvasculature. Although patients usually develop thrombocytopenia, MAHA, fever, confusion, and organ damage (eg, acute renal failure), the coagulation cascade is unaffected; therefore, PT/PTT and fibrinolysis (fibrinogen level) are normal, and bleeding does not occur.
(Choice D) Immune (idiopathic) thrombocytopenic purpura (ITP) is marked by autoantibodies to platelets/megakaryocytes; thrombocytopenia is the only peripheral blood abnormality. Coagulation studies (eg, PT, PTT) and fibrinogen levels are normal. Spontaneous bleeding is very uncommon unless the platelet count is <10,000/mm3.
(Choice E) The liver generates thrombopoietin and the majority of clotting factors. Therefore, patients with significantly impaired hepatic function (eg, cirrhosis) sometimes have mild thrombocytopenia and prolonged coagulation studies. However, fibrinogen level is usually normal and this patient has no other signs of advanced hepatic dysfunction (eg, ascites, jaundice).
Educational objective:
Disseminated intravascular coagulation commonly occurs in the setting of sepsis and is characterized by widespread activation of the coagulation cascade with formation of microthrombi. Laboratory results reveal prolonged PT/PTT, thrombocytopenia, and low fibrinogen (ie, a consumptive coagulopathy), and patients usually have signs of bleeding (eg, oozing from venipuncture sites).