- © 2003 by American Society of Clinical Oncology
Challenging Problems in Advanced Malignancy
CASE 2. DISSEMINATED INTRAVASCULAR COAGULATION IN METASTATIC HORMONE-REFRACTORY PROSTATE CANCER
A 70-year-old man was admitted to the hospital because of generalized ecchymoses. He had been diagnosed with prostate cancer metastatic to bone 5 years earlier. Subsequently, he had slowly progressive disease, despite a variety of endocrine maneuvers and treatment with mitoxantrone plus prednisone. He also received radiation therapy to his left shoulder and to epidural disease in the lower thoracic spine. Three months before this admission, he underwent posterolateral decompression and fusion for thoracic spinal cord compression. Within 24 hours of surgery, his platelet count dropped from 230,000/μL to 69,000/μL, and his prothrombin time increased to 19.1 seconds (International Normalized Ratio [INR] = 1.56). He was given packed red cells, platelets, and fresh frozen plasma, and he showed improvement in all hematologic parameters. Five weeks before this admission, his platelet count was 149,000/μL.
The most striking physical finding on this admission was multiple large confluent ecchymoses primarily involving the flanks and lower extremities (Fig 1⇓). There was no evidence of mucosal bleeding. His platelet count was 62,000/μL, and his prothrombin time was 14.8 seconds (INR = 1.21). The activated partial thromboplastin time was 32.6 seconds, the serum fibrinogen was 87 mg/dL (normal limits = 223 to 446 mg/dL), and the d-dimer level was 2 μg/mL (normal level = < 0.5 μg/mL). Shortly after admission, the fibrinogen dropped to 55 mg/dL, and the d-dimer level increased to 8 μg/mL. His coagulation factors improved with the administration of low-dose heparin by continuous infusion, cryoprecipitate, and platelets, in addition to estramustine phosphate. He was discharged on the sixth hospital day with a platelet count of 83,000/μL, normal prothrombin and activated partial thromboplastin times, a serum fibrinogen level of 195 mg/dL, and a D-dimer level of 1 μg/mL.
Despite the addition of weekly paclitaxel, he required several hospitalizations for recurring coagulopathy over the ensuing 6 weeks. Each time, there was transient improvement with heparin, cryoprecipitate, and transfusion of platelets. He was admitted for the last time on November 13, 2001, with a hemoglobin level of 6.9 g/dL and evidence of massive flank bleeding on computerized tomography. Further hematologic support was withdrawn at his request, and he died 6 days later.
Although laboratory evidence of abnormal coagulation is common in cancer patients, clinically evident bleeding is rare in patients with solid tumors.1 One study group recently reported on the occurrence of symptomatic disseminated intravascular coagulation (DIC) in 1,117 patients with solid tumors.2 Seventy-six patients (6.8%) had laboratory evidence of DIC and clinical evidence of altered hemostasis. Unknown primary cancers and cancers originating in the lung, breast, and prostate were responsible for almost half the cases. Gastrointestinal cancers (colorectal, gastric, and pancreatic) were responsible for another 22%. The majority of cancers were adenocarcinomas. Abnormal bleeding associated with prostate cancer was described as early as 1930.3 Other groups, in 19494 and the early 1950s,5 reported several cases of fibrinolysis in patients with prostate cancer. But it was only after the description of DIC by Rodriguez-Erdmann, in 1965,6 that the nature of this coagulopathy was understood. DIC, with or without overt bleeding, can be a presenting sign of prostate cancer.7,8 It may also occur as a result of the introduction of thromboplastic substances into the blood stream after biopsy of either a primary or metastatic site,7,10–,11 or it may develop as a manifestation of advanced disease. Treatment of this complication remains controversial because most reports are anecdotal and numbers of patients are small. Clotting factors, heparin, and platelets are commonly administered. Various forms of hormonal therapy, including high-dose stilbestrol and rapid induction of the castrate state with ketoconazole, have also been reported to be effective, at least in the hormone-naïve state.5,7–,14 Epsilon aminocaproic acid has been used in patients with excessive fibrinolysis,11 but this approach is controversial in the setting of DIC. Finally, there is at least one report of the beneficial effect of systemic chemotherapy with docetaxel, although the patients in this report received heparin and epsilon amino caproic acid as well.15
Like many of the cases reported in the literature, our patient initially developed DIC after an invasive surgical procedure. Later in the course of his illness, he had an intractable coagulopathy in which the fibrinolytic component predominated.
As more effective therapy for advanced prostate cancer becomes available and patients live longer, this complication can be expected to be encountered more frequently. Clinicians caring for patients with prostate cancer should maintain a high index of suspicion for clotting disorders and should be familiar with their diagnosis and management.
Patient presenting with multiple large confluent ecchymoses primarily involving the flanks and lower extremities.
