title: [Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure, mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case].
abstract: Disseminated intravascular coagulopathy (DIC) is characterized as activation of the clotting system resulting in fibrin thrombi, gradually diminishing levels of clotting factors with increased risk of bleeding. Basically two types of DIC are distinguished: (1) chronic (compensated) - with alteration of laboratory values and (2) acute (non-compensated) - with severe clinical manifestations: bleeding, shock, acute renal failure (ARF), transient focal neurologic deficit, delirium or coma. Chronic DIC related to metastatic neoplasia is caused by pancreatic, gastric or prostatic carcinoma in most of the cases. Incidence rate of DIC is 13-30% in prostate cancer, among those only 0.4-1.65% of patients had clinical signs and symptoms of DIC. In other words, chronic DIC is developed in one of eight patients with prostate cancer. DIC is considered as a poor prognostic factor in prostatic carcinoma. The similar clinical and laboratory findings of TTP-HUS (thrombotic thrombocytopenic purpura - hemolytic uremic syndrome) and DIC makes it difficult to differentiate between them. A 71 years old male patient with known chronic obstructive pulmonary disease, benign prostatic hyperplasia, significant carotid artery stenosis, gastric ulcer and alcoholic liver disease was admitted to another hospital with melena. Gastroscopy revealed intact gastric mucosa and actually non-bleeding duodenal ulcer covered by clots. Laboratory results showed hyperkalemia, elevated kidney function tests, indirect hyperbilirubinemia, increased liver function tests, leukocytosis, anemia, thrombocytopenia and elevated international normalized ratio (INR). He was treated with saline infusions, four units of red blood cells and one unit of fresh frozen plasma transfusions. Four days later he was transported to our Institution with ARF. Physical examination revealed dyspnoe, petechiae, hemoptoe, oliguria, chest-wall pain and aggressive behavior. Thrombocytopenia, signs of MAHA (fragmentocytes and helmet cells in the peripheral blood), normal INR, elevated lactate dehydrogenase (LDH) and ARF suggested TTP-HUS. Hemodialysis and six plasmaferesis (PF) were carried out. After the fifth PF, skin manifestations of thrombotic microangiopathy occurred on the feet. Clotting analysis revealed elevated D-dimer (>5 μg/mL), normal fibrinogen (3.2 g/L), a slightly raised INR (1.36) and activated partial prothrombin time (APTT) (45.8 sec), normal reticulocyte (57 G/L) and a slightly low platelet count (123 G/L), which proved to be chronic DIC. Therapeutic dose of low-molecular-weight heparin (LMWH) was started. Elevated prostate-specific antigen (PSA) (109.6 ng/mL) suggested prostatic carcinoma. Prostate biopsy revealed adenocarcinoma (Gleason: 4+4 for left lobe and 3+3 for right lobe). Elevated alkaline phosphatase suggested metastases in the bone, which were confirmed by bone scintigraphy. Combined androgen blockade (CAB) was started. After three months follow-up our patient's status is satisfactory. PSA is in the normal range (4.6 ng/mL). Thrombocytopenia of uncertain origin with normal or raised INR, APTT, elevated D-dimer, normal fibrinogen and reticulocyte count prove the diagnosis of chronic DIC. This process warrants searching for metastatic neoplasia. Due to the relatively low serum levels of circulating procoagulant factors (e.g. tissue factor), therapeutic dose of LMWH can be used with good efficiency in chronic DIC with low risk of bleeding. Severe DIC as a complication of metastatic prostate cancer can be treated by androgen deprivation therapy (ADT) or CAB in combination with ketokonazole and concomitant use of supportive treatment. Deme D, Ragán M, Kovács L, Kalmár K, Varga E, Varga T, Rakonczai E. Metastatic prostate cancer complicated with chronic disseminated intravascular coagulopathy causing acute renal failure mimicking thrombotic thrombocytopenic purpura and hemolytic uremic syndrome: pathomechanism, differential diagnosis and therapy related to a case.
authors.affiliation: Szent Lázár Megyei Kórház Belgyógyászati Osztály 3100 Salgótarján Füleki út 54-56.
authors.forename: Dániel
authors.initials: D
authors.lastname: Deme
authors.forename: Márton
authors.initials: M
authors.lastname: Ragán
authors.forename: Katalin
authors.initials: K
authors.lastname: Kalmár
authors.forename: Lajos
authors.initials: L
authors.lastname: Kovács
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Varga
authors.forename: Tünde
authors.initials: T
authors.lastname: Varga
authors.forename: Ervin
authors.initials: E
authors.lastname: Rakonczai
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000230:Adenocarcinoma / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary; D002908:Chronic Disease; D003937:Diagnosis, Differential; D004211:Disseminated Intravascular Coagulation / Q000150:complications / Q000175:diagnosis* / Q000628:therapy*; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal