Anticoagulant-resistant thrombophilia in a patient with polycythemia vera: a case report

Mechanical valve thrombosis is a rare condition in an adequately anticoagulated patient in the absence of underlying thrombophilia. We report a case of a 76-year-old male with mechanical prosthetic mitral valve thrombosis as the presenting feature of polycythemia vera. The patient was treated with thrombolysis at the time of acute presentation and subsequently maintained on low molecular weight heparin, low-dose aspirin, phlebotomy and hydroxyurea. Hemoglobin, leucocytosis and platelet count were controlled for almost 4 years after which the patient suffered a second, fatal episode in the setting of therapeutic anti-Xa level. This case report highlights the thrombotic risks associated with polycythemia vera. The proposed mechanisms of hypercoagulability in polycythemia vera are reviewed. To the best of our knowledge, mechanical valve thromboses as the presenting feature of polycythemia vera has not been reported previously.     

Isolated cerebellar infarction as a presenting symptom of polycythemia vera.

Although polycythemia vera is one of the reported causes for cerebral infarction, isolated cerebellar infarction, a rare disorder, was never reported in combination with polycythemia vera. This is a report of a 72-year-old woman in whom isolated cerebellar infarction was the presenting manifestation of polycythemia vera. The patient was treated with recurrent phlebotomies until the hematocrit decreased to < 45%. This treatment was followed by marked neurological improvement. A better awareness of the possibility of cerebellar infarction in polycythemia vera may disclose additional cases.     

35-year-old patient with metastasized carcinoid of Vater's ampulla--case report and review of the literature]

We report the case of a 35-year-old female patient with a metastasized carcinoid of the papilla of Vater which is a rare lesion. 96 cases have been published in world literature previously. The carcinoid of the papilla of Vater appears typically as a hormone inactive tumor. It becomes symptomatic by cholestasis and jaundice in most cases and not by carcinoid-syndrome. An association with von Recklinghausen's disease as described in 25% of cases was not given in our patient. In contrast to the duodenal carcinoid there is no linear relationship between primary tumor size and incidence of metastases. The correct diagnosis was proven by histologic and immunohistochemical methods on specimen taken after endoscopic papillotomy. In spite of sensitive diagnostic methods like endosonography and somatostatin-receptor-scintigraphy exact staging was made intraoperatively in this case. Three months after pylorus pancreatoduodenal resection with lymphadenectomy the patient remained well with no evidence of tumor recurrence.     

Cyanotic Congenital Heart Disease (CCHD) with Symptomatic Erythrocytosis

Secondary erythrocytosis of cyanotic congenital heart disease (CCHD) is pathologically different from primary erythrocytosis of polycythemia vera (PV). An association between elevated hematocrit and thrombosis has been established in PV patients, and treatment guidelines recommend maintaining hematocrit <45%. Although an association between elevated hematocrit and thrombosis has not been established in CCHD and secondary erythrocytosis, the current clinical practice is to phlebotomize these patients to hematocrit <65%. We report a 21-year-old woman with CCHD who presented with symptomatic erythrocytosis with numbness and tingling with hemoglobin 25.2 g/dl and hematocrit 75.8%. Her symptoms resolved with IV hydration. Other factors, including dehydration and iron deficiency, may precipitate hyperviscosity symptoms. The treatment is volume replacement and low-dose iron therapy, not phlebotomy. Repeated phlebotomy causes iron deficiency with microcytic erythrocytes, which increases the whole blood viscosity and, therefore, can potentially accentuate rather than decrease the risk for a cerebrovascular accident.     

Delayed manifestation and slow progression of cerebral infarction caused by polycythemia rubra vera

BACKGROUND: Polycythemia rubra vera is often found after the manifestation of cerebral infarction, though the pathogenesis is still controversial. We present a case of cerebral infarction secondary to polycythemia rubra vera, which presented a slow expansion on magnetic resonance imaging despite severe hemiplegia. This case suggests a possible mechanism for development of cerebral infarction in polycythemia rubra vera. METHODS: This case report was conducted in a university hospital. Magnetic resonance imaging and diffusion-weighted imaging were performed to assess the evolution of infarction, and the total blood volume and cerebral blood flow were determined with the use of isotopes, Cr and Tc, respectively. Phlebotomy was performed, but intervention was not applicable. The manual muscle test and sensory disturbance were assessed by the same physiotherapist throughout the clinical course. RESULTS: A 64-year-old male patient with polycythemia rubra vera had a cerebral infarction. A subtle change was observed on CT scan on the third day after the onset of infarction, and a small signal was demonstrated on magnetic resonance imaging on the fourth day. The cerebral infarction expanded slowly in size and reached a maximum on day 24. A diagnosis of cerebral infarction secondary to polycythemia rubra vera was made, and treatment by phlebotomy, hydration, and hydroxyurea was begun. Though the hemiplegia remained, he became ambulatory with a brace, as do patients with atherosclerotic infarction. CONCLUSIONS: It is suggested that the delayed manifestation and slow expansion of cerebral infarction caused by elevated hematocrit might be derived from a pathogenesis different from atherosclerotic infarction.     

Malignant carcinoid tumor in the papilla of Vater: case report and review of 25 cases reported in Japan

Carcinoid tumors in the papilla of Vater are rare. We describe a 48-year-old male who was diagnosed with a tumor consisting of atypical cells in the papilla of Vater. He underwent curative resection of the tumor by pancreatico-duodenectomy (PD), with dissection of the regional lymph nodes. Microscopic examination revealed a metastatic lymph node in the pancreatic region. Characteristic findings on histopathological and electron microscopic studies led to the final diagnosis of malignant carcinoid tumor. It is clear from the literature that carcinoid tumors in the papilla of Vater metastasize to the regional lymph nodes and the liver. However, it has been difficult to preoperatively diagnose carcinoid tumor in the papilla of Vater. Therefore, if we observe atypical cells in the papilla of Vater, malignant carcinoid tumor should be considered. If this tumor is suspected, PD or pylorus-preserving PD, together with dissection of the regional lymph nodes, at least along the hepatoduodenal ligament, should be considered as the treatment of first choice.     

Occlusion of the superior mesenteric artery in a patient with Polycythemia vera: Resolution with percutaneous transluminal angioplasty

The case is reported of a 46-year-old male patient with polycythemia vera (PV) treated with phlebotomy who developed an occlusive thrombosis of the superior mesenteric artery 2 years after the diagnosis. He was successfully managed with percutaneous transluminal angioplasty. The patient did not develop any other thrombotic phenomena. To our knowledge, there are no previous reports on the use of percutaneous transluminal angioplasty in the management of arterial thrombotic complications in PV patients.     

Pheochromocytoma, polycythemia, and venous thrombosis

Polycythemia is rarely associated with pheochromocytoma. A patient with a 22-year history of malignant pheochromocytoma is presented in whom major complications developed as a result of long-standing polycythemia, apparently due to secretion of erythropoietin by the tumors. Despite attempts to reduce tumor burden by surgery, chemotherapy, and large doses of I-131-metaiodobenzylguanidine, polycythemia persisted. Extensive venous thrombosis developed requiring hospitalization and anticoagulation. Thus, polycythemia itself may be a cause of major morbidity in patients with pheochromocytoma, and prophylactic measures may be warranted. Review of the 130 patients with benign and malignant pheochromocytoma studied since the introduction of I-131-metaiodobenzylguanidine in 1980 revealed another six patients with hematocrits over 50 but only one had a hematocrit greater than 55 and required regular phlebotomy. In contrast, anemia (hematocrit less than 35) due to variety of causes was present in 18 cases.     

Polycythemia vera in childhood: Case report and review of the literature

A patient presented at 5 years of age with polycythemia vera. He subsequently developed splenic infarctions and died at 20 years of age following cerebral hemorrhage and infarctions. Two months before his death, he developed hypertension and had biochemical evidence of primary hyperparathyroidism and possibly pheochromocytoma. Only nine reported childhood cases of polycythemia vera fulfill the criteria of the Polycythemia Vera Study Group. These cases are summarized and the complications discussed. Although none have progressed to myeloid metaplasia or acute leukemia, these patients are at risk of developing thrombo-hemorrhagic complications; available evidence indicates that they should be managed to keep the hematocrit between 40 and 45%.     

Oxaliplatin-based chemotherapy for the treatment of a metastatic carcinoid tumor

Carcinoid tumors are rare and often resistant to chemotherapy agents. Although a slow-growing tumor, patients can have significant morbidity associated with carcinoid syndrome and patients will often die as a result of tumor progression. We report the first case of a patient with a metastatic carcinoid tumor to respond to an oxaliplatin-based regimen. Further studies are needed to validate this observation.     

Phase II open label trial of imatinib in polycythemia rubra vera

Polycythemia rubra vera is a chronic myeloproliferative disorder characterized by panmyelosis with the resultant potential for thrombosis, myelofibrosis, and acute leukemia. Treatment has rested on phlebotomy and hydroxyurea. In 2002, we reported two patients who were unable to tolerate hydroxyurea but responded to imatinib mesylate (Gleevec). These patients have remained in complete hematologic remission on imatinib since 1999. As a result we began a phase II, open label trial of imatinib in patients with polycythemia vera. Patients meeting the Polycythemia Vera Study group criteria for the diagnosis of polycythemia vera, either naïve or intolerant to prior treatment were allowed to enroll. Initial therapy was begun with imatinib mesylate at 400 mg a day and two dose escalations, one to 600 and second to 800 mg a day, were allowed for patients not achieving a target hematocrit of 44 or less; or a platelet count of less than 600,000/mm³. Twenty patients were enrolled, 15 achieved complete hematologic remission within 12 weeks and ten remain on study. Six patients remain in remission on 400 mg a day and four on 500 mg a day. Gastrointestinal or cutaneous toxicities were primarily grade I or II. All patients were negative for bcr/abl. Imatinib mesylate is capable of producing hematologic remission in the majority of patients with polycythemia vera and provides another option for patient management, particularly in those intolerant to hydroxyurea.     

Evidence-based management of polycythemia vera

The clinical course of polycythemia vera is marked by significant thrombotic complications and a variable risk of the disease turning either into myeloid metaplasia with myelofibrosis or into acute myeloid leukemia. Cytoreductive treatment of blood hyperviscosity by phlebotomy or chemotherapy and antiplatelet therapy with low-dose aspirin have dramatically reduced the number of thrombotic complications and substantially improved survival. However, there is concern that certain myelosuppressive drugs accelerate the disease progression to acute leukemia. Thus, the objective of management is two-fold: first, to minimize the risk of thrombotic complications; second, to prevent progression to myelofibrotic or leukemic transformation. This chapter provides updated estimates of the risk of thrombosis and disease progression and evaluates the various randomized and observational studies in polycythemia vera, according to an evidence-based approach.     

Testicular metastasis from ileal carcinoid: report of a case

PURPOSE: This report presents a patient with testicular metastasis from an ileal carcinoid. METHODS: This was a retrospective case review with literature review. RESULTS: The patient underwent right orchiectomy for a solid mass. Pathology revealed carcinoid tumor. Octreotide scan showed increased concentration in the right lower quadrant of the abdomen. Computerized tomography results were negative. Colonoscopy with biopsy revealed carcinoid of the terminal ileum. The patient underwent an elective resection of the terminal ileum and the right colon. Pathology revealed carcinoid tumor with vascular and lymphatic invasion present, and eight lymph nodes were positive. The patient had adjuvant treatment with octreotide. CONCLUSION: Carcinoid tumors have been reported to metastasize to numerous areas. This is the first report of testicular metastasis from ileal carcinoid. Primary carcinoids of the testicle have been reported also. The clinician should be aware of this rare metastatic event. When pathology reveals carcinoid of the testicle, metastatic disease should be excluded before the tumor is identified as primary.     

Familial polycythemia vera with Budd-Chiari syndrome in childhood

Polycythemia vera is a myeloproliferative disorder that, in most cases, occurs sporadically with a median age at presentation of 60 years. Familial cases are very rare and usually manifest in elderly family members. The Budd-Chiari syndrome, characterized by the obstruction and occlusion of the suprahepatic veins, is a rare typical complication in polycythemia vera patients. To date, only two children or adolescents with polycythemia vera and Budd-Chiari syndrome have been described. Here, we report an 11-year-old girl with Budd-Chiari syndrome as the initial symptom of familial polycythemia vera, which was also found in the girl's grandmother. Details of the diagnostic procedures used and the clinical course are reported. The patient underwent orthotopic liver transplantation and is being treated with hydroxyurea. The available literature on familial polycythemia vera and polycythemia vera in childhood with and without Budd-Chiari syndrome is reviewed.     

Aspirin-responsive painful red,blue, black toe,or finger syndrome in polycythemia vera associated with thrombocythemia

Five patients with red, purple blue, or black toes or fingers due to thrombocythemia associated with polycythemia vera (polycythemia and thrombocythemia vera) in four and essential thrombocythemia (thrombocythemia vera) in one are described. The microvascular erythromelalgic syndrome of thrombocythemia was overlooked and progressed to cold blue swollen and painful fingers or black toes in three patients with polycythemia and thrombocythemia vera due to arteriographically documented occlusions of digital or large peripheral arteries with no evidence of preexistent atherosclerotic vascular disease. Concomitant erythromelalgia of the hand palm could be confirmed by the histopathological findings of arteriolar thrombotic lesions in the reticular dermis in two patients with polycythemia and thrombocythemia vera. The increased hematocrit in the presented patients with polycythemia and thrombocythemia vera contributed to the progression of the microvascular syndrome of thrombocythemia to major occlusive ischemic events of the extremities. Standard therapy with oral anticoagulants and reduction of the hematocrit to normal by bloodletting did not affect the platelet-mediated microvascular erythromelalgic, ischemic symptoms in the patients with polycythemia vera because thrombocythemia vera persisted. Complete relief of pain and restoration of the ischemic acral circulation disturbances in patients with thrombocythemia vera or thrombocythemia associated with polycythemia vera in maintained remission by bloodletting could be obtained by long-term treatment with low-dose aspirin.     

Polycythemia vera presenting as acute myocardial infarction: An unusual presentation

Acute myocardial infarction (AMI) is usually seen in the setting of atherosclerosis and its associated risk factors. Myocardial infarction in the young poses a particular challenge, as the disease is less likely, due to atherosclerosis. We report the case of a 37-year-old female patient who presented with ST segment elevation anterolateral AMI. The only abnormality on routine blood investigation was raised hemoglobin and hematocrit. After further testing, she was diagnosed according to the World Health Organization (WHO) criteria with polycythemia vera. This case illustrates the importance of recognizing polycythemia vera as an important cause of thrombosis, which can present initially as AMI, and to emphasize the early recognition of the disease in order to initiate appropriate management strategies.     

Role of interferon alpha-2a in the treatment of polycythemia vera

We studied the effects of recombinant interferon alpha-2a (IFN-alpha) in 36 patients with polycythemia vera (PV) previously treated with phlebotomy and/or conventional cytostatic agents. In each patient, after at least 2 months of discontinuation of any cytotoxic therapy, the hematocrit (Hmt) was first brought to normal value by phlebotomy; IFN-alpha treatment was then begun at a starting dose of 3,000,000 IU s. c. three times a week. Response to treatment, which was assessed monthly, was defined as persistent normalization of Hmt without concomitant phlebotomy; in non-responsive patients the initial IFN-alpha weekly dosage was progressively increased. Twenty patients were responsive with a median duration of response of 7 months (range 2-25+ months); out of these, 7 patients are still under treatment and responsive at 13+, 17+, 20+, 22+, 23+, 25+, 25+ months. These findings indicate that a cohort, although small, of patients with PV (19.4%) are persistently sensitive to IFN-alpha; in this subset of patients, this cytokine can therefore provide a useful treatment option, since, contrary to conventional therapeutic approaches such as radioactive phosphorus, cytostatic agents, or phlebotomy, IFN-alpha is devoid of harmful side effects. ©1995 Wiley-Liss, Inc.     

The effect of interferon alpha on myeloproliferation and vascular complications in polycythemia vera

Abstract: The effect of interferon alpha (IFN) on myeloproliferation and vascular complications was studied in 32 patients (17 female, 15 male; median age 60.5 yr) with polycythemia vera (PV). IFN therapy was initiated at a median time of 19 months after diagnosis. Ten patients were pretreated with chemotherapy in addition to phlebotomy. IFN dose was 12 megaU/wk during the first year, 9 megaU/wk during the second year and 12 megaU/wk thereafter. During IFN alpha treatment hematocrit level was 45.7% and remained at this level after the second year of treatment, compared to 46.5% before IFN. The frequency of phlebotomy before IFN was 0.49/month and dropped to 0.19/month (p<0.0005) during the first year of IFN treatment. IFN normalized high platelet and leukocyte counts in a majority of patients. The incidence of deep venous thromboses was 3.6%/yr before IFN alpha and 1.8%/yr during the first year of treatment. IFN-induced side-effects were mainly flu-like symptoms, fever, fatigue and arthralgia. In conclusion, IFN allowed the reduction of the dose of chemotherapy and decreased the need of phlebotomy. Despite improvement of hematological parameters, it is still uncertain whether IFN alpha can improve clinical symptoms in PV.     

Recombinant interferon α-2b in the treatment of polycythemia vera

We studied the effects of recombinant α2-b interferon (α2-b IFN) in a dose of 3 × 10⁶U intramuscularly three times a week for 1 year in 13 patients affected by polycythemia vera (PV) previously treated with phlebotomy only. Response to treatment was evaluated by reduction of the number of phlebotomies required to retain normal hematocrit value. Ten out of 13 patients (77%) responded to treatment; in 4 of them the exigency of phlebotomy was completely eliminated. In all responders a concomitant decrease of platelet count and splenomegaly was obtained. Treatment was well tolerated and side effects were easily controlled. We conclude that α-IFN may represent an attractive therapeutic option in the management of the proliferative stages of PV. © 1993 Wiley-Liss, Inc.     

Treatment of the myeloproliferative disorders with 32P

Abstract: The use of radioactive phosphorus (³²P) to treat the myeloproliferative disorders (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939 when John H. Lawrence treated the first patient on the basis of work done in the laboratory anima that found localization of the radioisotope in the spleen, liver, bone and in leukemic cells sufficient to indicate a therapeutic potential. After World War II when ³²P became widely available, it was used extensively to treat the chronic leukemias and polycythemia vera. Its use in the treatment of essential thrombocythemia began later in 1950. Today it is not widely used in the treatment of the chronic leukemia, if at all, its use in polycythemia vera appears to have decreased substantially and replaced by hydroxyurea, and its use in the management of essential thrombocythemia is not widespread. In each instance it has been replaced by a drug developed for use in cancer chemotherapy, and in some instances by interferon. It probably has wider use in polycythemia vera in the rest of Western Europe than in the UK, and there are cogent reasons to suggest that it may be the best tool for the treatment of polycythemia vera. Thus have we discarded a treatment modality that in polycythemia vera may be the best?