Use of Low Molecular Weight Heparin and Aminocaproic Acid in Chronic DIC Associated with Prostate Cancer- A Case Report
TSW Urology
1537-744X
Use of Low Molecular Weight Heparin and Aminocaproic Acid in Chronic DIC Associated with Prostate Cancer- A Case Report
Keisuke Shirai 1 2
Uzair B. Chaudhary 1 2
0 /mm , 3 fibrinogen was less than 60 mg/dl, International Normalized Ratio (INR) 2.2, PT 24 seconds, PTT 33 seconds and serum creatinine 0.8 mg/dl
1 A fifty four-year old African American male with metastatic AIPC was admitted to our hospital with history of 4-5 days of epistaxis and fatigue. Physical examination was unremarkable. Laboratory work-up revealed a white blood cell count of 10x 10
2 Department of Medicine, Division of Hematology/Oncology, Medical University of South Carolina , Charleston, SC , USA
Disseminated Intravascular Coagulopathy (DIC) is the most common coagulopathy in patients with prostate cancer. Though rare, it could be fatal without treatment. Literature suggests that there is significant activation of fibrinolytic pathway. Pathophysiology of DIC in patients with prostate cancer is not completely understood. We present here a case of chronic DIC in a patient with metastatic androgen independent prostate cancer. His DIC was managed successfully with a combination of aminocaproic acid and low weight molecular heparin. The use of low molecular weight heparin may make management of chronic DIC in prostate cancer more feasible in an out patient setting.
DIC; prostate cancer; aminocaproic acid; low molecular weight heparin
INTRODUCTION
He was initially diagnosed with prostate cancer in 1997 with a Gleason score of 8 and a serum
prostate specific antigen (PSA) of greater than 50 ng/ml. He was treated with leuprolide and external
beam radiation therapy. Initially, his PSA became undetectable, but in 2000 it began to rise. Combined
androgen blockade with leuprolide and bicalutamide was reinitiated with minimal response. In 2001,
despite use of ketoconazole treatment, his PSA continued to rise and he was found to have bone metastase
in the thoracic and lumber spine.
Hospital course
He was supported with packed red blood cells, platelets, and cryoprecipitate. He was started on weekly
docetaxel (35mg/m2), on a day 1, 8 schedule every three weeks. He required daily platelet transfusions
and cryoprecipitate to maintain his platelet count above 30x103/mm3 and fibrinogen of more than 100
mg/dl. With the initiation of docetaxel treatment, epistaxis resolved with an improvement in his
coagulation parameters. After 72 hours he was discharged to home.
Unfortunately 1 week later, he was readmitted to the hospital with epistaxis. At this time fibrinogen
was again less than 100 mg/dl with prolonged PT/PTT. To control bleeding, he was treated with 2 g every
6 hours of aminocaproic acid along with subcutaneous low molecular weight heparin (LMWH) 30 mg
twice a day. With this combination his platelet and fibrinogen were stabilized in two days (Figure 1). At
the time of discharge the dose of aminocaproic acid was tapered to 1 g every 6 hours. The patients DIC
parameters were under control for three months with aminocaproic acid at 500 mg every 6 hours and
LMWH at 30 mg twice a day without any evidence of bleeding or thrombosis.
DISCUSSION
Although pathogenic mechanisms of DIC in prostate cancer are not well understood, an overly activated
fibrinolytic pathway is thought to be the cardinal feature of this condition[1,2]. Fibrinolytic bleeding
could also be seen in other neoplastic diseases such as carcinoma of the lung, stomach, and cervix. With
an activated fibrinolytic pathway patients can have fatal bleeding. Early recognition of DIC is essential to
avoid a fatal course.
Several treatment approaches to control DIC in prostate cancer have been described in the past.
Needless to say, the most important treatment is to control underlying disease. Chemotherapy with
docetaxel or mitoxantrone plays a key role in metastatic AIPC[3,4]. A variety of hormonal maneuvers
including DES[5,6] and ketoconazole[7,8] have been used with limited success. Several successful case
reports with radioactive agents including samarium 153 have been reported with limited success[9].
The patient reported here responded initially to treatment with docetaxel only for a short period of
time. However, he was readmitted with bleeding and abnormal coagulation parameters. He required
multiple cryoprecipitate and platelet infusions to control bleeding and maintain fibrinogen level above
100 mg/dl.
In 1992, Cooper et al. reported a successfully treated DIC case in prostate carcinoma with
aminocaproic acid and low dose heparin continuous infusion (300-500units/hour)[10]. Aminocaproic acid
was chosen to control an overactivated fibrinolytic pathway and at the same time low dose heparin was
given to compensate for the hypercoagulable state induced by aminocaproic acid. As far as we know, this
is the only case report of DIC in prostate cancer effectively treated with aminocaproic acid.
Aminocaproic acid is 6-aminohexanoic acid, which acts as an inhibit (...truncated)