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PO-73 Prevalence of cancer and congenital thrombophilia in 435 patients with acute venous thromboembolism (VTE)
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4th Int. Conf. on Thrombosis and Hemostasis Issues in Cancer / Thrombosis Research 120 Suppl. 2 (2007) S145–S178
PO-72 A rare case of portal vein thrombosis complicating juvenile idiopathic myelofibrosis with intrahepatic haematopoiesis
PO-73 Prevalence of cancer and congenital thrombophilia in 435 patients with acute venous thromboembolism (VTE)
S. Pulini1 *, R. Di Lorenzo1 , A.M. Morelli1 , E. D’Amico2 , M. Mereu3 , R. Basilico3 , G. Fioritoni1 . 1 Department of Hematology, “Spirito Santo” Hospital, Pescara; 2 Department of Internal Medicine, Liver Unit, “Spirito Santo” Hospital, Pescara; 3 Department of Radiology, “SS. Annunziata” Hospital, University of Chieti, Italy
A. Achkar1,2 *, M.H. Horellou1 , X. Leclercq2 , Y. Lambert2 , otel-Dieu Hospital, J. Conard1 , J.P. Laaban1 , M.M. Samama1 . 1 Hˆ Paris; 2 Hˆ opital de Beauvais, France
Introduction: Idiopathic myelofibrosis (IMF) and portal vein thrombosis (PVT) are rare in young adults. Aim: We describe an unusual case of juvenile IMF, with a clinical history beginning at the age of 2 yrs and lasting more than 20 yrs, complicated by PVT. Some possible determinants of hypercoagulability and PVT, the prognosis and the problematic management of such rare a case are here discussed. Patient and Methods: A girl was referred for isolated thrombocytosis (700,000/ml) since she was 2 yrs old. The bone marrow was hypercellular, with clusters of megakaryocytes and fibrosis. A watch-and-wait strategy seemed appropriate, platelet remaining moderately elevated in about 20 years; low-dose aspirin was finally started. Results: At 23 yrs, the thrombocytosis and the splenomegaly both increased (1,900,000/ml and 90 cm2 ) with leucocytosis (18,000/ml), without anemia. The biopsy showed IMF grade I. The complete thrombophilic study resulted negative; leukocytic alkaline phosphatase was high, EPO-independent BFU-E were present, there weren’t cytogenetic abnormalities, but V617F JAK2 mutation in heterozygous state. The patient started anagrelide therapy. Some weeks before starting it, she had developed an asymptomatic increase of cholestatic indexes. A magnetic resonance imaging and the Doppler color flow imaging demonstrated splenomegaly, multiple splenic infarcts, hepatic patologic areas resulting hypointense in T2 weighted and hyperintense in T1-W images without nodular lesions; in the pancreatic area numerous convolute blood vessels going towards spleno-mesenteric-portal convergence to constitute a portal cavernoma associated to multiple collateral venous circles with fibrotic transformation of portal vein and filiform splenic vein with reduced blood flow. The fine needle hepatic biopsy showed focal intrahepatic extramedullary haematopoiesis (IEH). Gastroscopy didn’t reveal ulcerative lesions or varices. A bone marrow trephine biopsy showed progressive IMF grade II, with cluster of distrofic megakaryocytes with hyperlobulated forms and increased fibrosis, intravascular hemopoiesis. Hydroxyurea and warfarin were started; a research for allogeneic HSCT has been activated. Conclusion: IMF clinical course and prognosis are variable; this patient belongs to a low risk group according to Cervantes scoring system for young IMF people but represents a clinical progressive disease, because of IEH, multiple splenic infarcts, PVT. In such a case the choice of the cytoreductive drug and the decision about an anticoagulant therapy/prophylaxis are problematic, and the therapeutic option of HSCT, that is the only curative option but is associated with significant morbidity and mortality, is still controversial. In this young patient the reduced hepatopetal flow, for the sinusoidal obstruction given by the focal IEH, constituted a predisposing factor for PVT; moreover the JAK2 mutation is frequently found in PVT. Anagrelide is promising for young people; it has been changed to hydroxyurea, because this has a major efficacy in preventing VT and reducing marrow fibrosis and splenomegaly; a long term leukemogenic effect hasn’t been demonstrated. Warfarin was started mainly as a secondary prophylaxis; it isn’t clear the best duration of oral anticoagulation (long life?) since IMF itself is an important and above all persistent VT risk factor.
Background: Relationship between symptomatic venous thromboembolism and occult malignant disease is generally accepted but still controversial and there is no consensual recommendation for thrombophilia screening. Objectives: To determine the frequency of malignant disease (known and unknown) and the prevalence of congenital and acquired thrombophilia in patients hospitalized with acute VTE. Methods: We studied 435 consecutive patients enrolled into two centers [214 women, 221 men, mean age 55±15; patients <40 y.o. n = 85 (20%) or >40 y.o. n = 350 (80%)] with VTE confirmed by objective tests. 296 patients had one or more previous VTE. They were investigated for congenital thrombophilia and cancer. Tests for detection of Antithrombin (AT), Protein C (PC), Protein S (PS) and antiphospholipid antibodies syndrome (APA) were performed in 394 (91%) patients. Factor V Leiden (FVL) and Prothrombin G20210A (FII) mutations were studied in 321 (74%) and 288 patients (66%) respectively. Results: A known cancer was present in 63 patients (15%). An unknown cancer was discovered in 25 patients (5.75%) after hospital admission, all of them in patients >40 y.o. Thrombophilia was present in 92 patients (21%) among them 16 were previously known: 10 AT (2.5%), 8 PC (2%) and 17 PS (4.3%) deficiency, and 8 (2%) APA, 41 inherited APC resistance due to FVL mutation (12.7%), heterozygous in 39 and homozygous in 2, and 19 (6.6%) FII mutation. A combined thrombophilia was present in 12 patients. Thrombophilia had been detected before the present episode in 4 patients for AT, in 5 patients for PC, in 7 patients for PS, in 4 patients for APA and in 6 patients for FVL. Only one patient with previously known cancer had FVL. Among 85 patients <40 y.o. thrombophilia was present in 48 (56%), 24 with FVL or FII mutation. Among 350 patients >40 y.o. thrombophilia was present in 42 (12%), 31 with FVL or FII mutation. In conclusion: The frequency of unknown cancer was relatively high in patients with acute VTE >40 years of age, suggesting that screening for occult cancer seems justified in this group of patients. Hereditary thrombophilia was 4.5 times more frequent in patients <40 y.o. than in those >40 y.o. while cancer was absent in patients <40 y.o. However, in patients with FVL and/or FII mutation, acute VTE was more frequently observed after 40 years of age than in patients with AT, PC and PS deficiency, suggesting that all thrombophilias are not the same. The usefulness of screening patients for congenital thrombophilia is suggested in view of its high prevalence. PO-74 Hypercoagulability in multiple myeloma A.D. Petropoulou1 *, G.T. Gerotziafas2 , E. Verdy2 , F. Rendu3 , M.M. Samama1 , M. Hatmi1 , I. Elalamy2 . 1 Service d’H´ ematologie opital Tenon UPMC Paris VI, 3 UMR 7131, Biologique, Hˆ otel-Dieu; 2 Hˆ Hˆ opital Broussais, Paris, France Introduction: We used the Thrombin Generation test (TGT) and measured the plasma levels of soluble thrombomodulin (sTM) to better clarify the multiple myeloma (MM) and thalidomide-related hypercoagulability. Methods: TGT was performed in citrated frozen platelet poor plasma (PPP). Blood was obtained from 22 MM, stage III, patients, 60.8 years old (42 77), 8 treated with thalidomide (T) (200 mg/d) and dexamethasone (D) (40 mg/d for 4 days) (TD group) and 14 receiving no treatment (MM group). 20 healthy volunteers formed the control group. Thrombin Generation (TG) was initiated by adding the PPP reagent (tissue factor and phospholipids) and the triggering solution (CaCl2 and fluorogenic substrate). The analyzed
4th Int. Conf. on Thrombosis and Hemostasis Issues in Cancer / Thrombosis Research 120 Suppl. 2 (2007) S145–S178
PO-72 A rare case of portal vein thrombosis complicating juvenile idiopathic myelofibrosis with intrahepatic haematopoiesis
PO-73 Prevalence of cancer and congenital thrombophilia in 435 patients with acute venous thromboembolism (VTE)
S. Pulini1 *, R. Di Lorenzo1 , A.M. Morelli1 , E. D’Amico2 , M. Mereu3 , R. Basilico3 , G. Fioritoni1 . 1 Department of Hematology, “Spirito Santo” Hospital, Pescara; 2 Department of Internal Medicine, Liver Unit, “Spirito Santo” Hospital, Pescara; 3 Department of Radiology, “SS. Annunziata” Hospital, University of Chieti, Italy
A. Achkar1,2 *, M.H. Horellou1 , X. Leclercq2 , Y. Lambert2 , otel-Dieu Hospital, J. Conard1 , J.P. Laaban1 , M.M. Samama1 . 1 Hˆ Paris; 2 Hˆ opital de Beauvais, France
Introduction: Idiopathic myelofibrosis (IMF) and portal vein thrombosis (PVT) are rare in young adults. Aim: We describe an unusual case of juvenile IMF, with a clinical history beginning at the age of 2 yrs and lasting more than 20 yrs, complicated by PVT. Some possible determinants of hypercoagulability and PVT, the prognosis and the problematic management of such rare a case are here discussed. Patient and Methods: A girl was referred for isolated thrombocytosis (700,000/ml) since she was 2 yrs old. The bone marrow was hypercellular, with clusters of megakaryocytes and fibrosis. A watch-and-wait strategy seemed appropriate, platelet remaining moderately elevated in about 20 years; low-dose aspirin was finally started. Results: At 23 yrs, the thrombocytosis and the splenomegaly both increased (1,900,000/ml and 90 cm2 ) with leucocytosis (18,000/ml), without anemia. The biopsy showed IMF grade I. The complete thrombophilic study resulted negative; leukocytic alkaline phosphatase was high, EPO-independent BFU-E were present, there weren’t cytogenetic abnormalities, but V617F JAK2 mutation in heterozygous state. The patient started anagrelide therapy. Some weeks before starting it, she had developed an asymptomatic increase of cholestatic indexes. A magnetic resonance imaging and the Doppler color flow imaging demonstrated splenomegaly, multiple splenic infarcts, hepatic patologic areas resulting hypointense in T2 weighted and hyperintense in T1-W images without nodular lesions; in the pancreatic area numerous convolute blood vessels going towards spleno-mesenteric-portal convergence to constitute a portal cavernoma associated to multiple collateral venous circles with fibrotic transformation of portal vein and filiform splenic vein with reduced blood flow. The fine needle hepatic biopsy showed focal intrahepatic extramedullary haematopoiesis (IEH). Gastroscopy didn’t reveal ulcerative lesions or varices. A bone marrow trephine biopsy showed progressive IMF grade II, with cluster of distrofic megakaryocytes with hyperlobulated forms and increased fibrosis, intravascular hemopoiesis. Hydroxyurea and warfarin were started; a research for allogeneic HSCT has been activated. Conclusion: IMF clinical course and prognosis are variable; this patient belongs to a low risk group according to Cervantes scoring system for young IMF people but represents a clinical progressive disease, because of IEH, multiple splenic infarcts, PVT. In such a case the choice of the cytoreductive drug and the decision about an anticoagulant therapy/prophylaxis are problematic, and the therapeutic option of HSCT, that is the only curative option but is associated with significant morbidity and mortality, is still controversial. In this young patient the reduced hepatopetal flow, for the sinusoidal obstruction given by the focal IEH, constituted a predisposing factor for PVT; moreover the JAK2 mutation is frequently found in PVT. Anagrelide is promising for young people; it has been changed to hydroxyurea, because this has a major efficacy in preventing VT and reducing marrow fibrosis and splenomegaly; a long term leukemogenic effect hasn’t been demonstrated. Warfarin was started mainly as a secondary prophylaxis; it isn’t clear the best duration of oral anticoagulation (long life?) since IMF itself is an important and above all persistent VT risk factor.
Background: Relationship between symptomatic venous thromboembolism and occult malignant disease is generally accepted but still controversial and there is no consensual recommendation for thrombophilia screening. Objectives: To determine the frequency of malignant disease (known and unknown) and the prevalence of congenital and acquired thrombophilia in patients hospitalized with acute VTE. Methods: We studied 435 consecutive patients enrolled into two centers [214 women, 221 men, mean age 55±15; patients <40 y.o. n = 85 (20%) or >40 y.o. n = 350 (80%)] with VTE confirmed by objective tests. 296 patients had one or more previous VTE. They were investigated for congenital thrombophilia and cancer. Tests for detection of Antithrombin (AT), Protein C (PC), Protein S (PS) and antiphospholipid antibodies syndrome (APA) were performed in 394 (91%) patients. Factor V Leiden (FVL) and Prothrombin G20210A (FII) mutations were studied in 321 (74%) and 288 patients (66%) respectively. Results: A known cancer was present in 63 patients (15%). An unknown cancer was discovered in 25 patients (5.75%) after hospital admission, all of them in patients >40 y.o. Thrombophilia was present in 92 patients (21%) among them 16 were previously known: 10 AT (2.5%), 8 PC (2%) and 17 PS (4.3%) deficiency, and 8 (2%) APA, 41 inherited APC resistance due to FVL mutation (12.7%), heterozygous in 39 and homozygous in 2, and 19 (6.6%) FII mutation. A combined thrombophilia was present in 12 patients. Thrombophilia had been detected before the present episode in 4 patients for AT, in 5 patients for PC, in 7 patients for PS, in 4 patients for APA and in 6 patients for FVL. Only one patient with previously known cancer had FVL. Among 85 patients <40 y.o. thrombophilia was present in 48 (56%), 24 with FVL or FII mutation. Among 350 patients >40 y.o. thrombophilia was present in 42 (12%), 31 with FVL or FII mutation. In conclusion: The frequency of unknown cancer was relatively high in patients with acute VTE >40 years of age, suggesting that screening for occult cancer seems justified in this group of patients. Hereditary thrombophilia was 4.5 times more frequent in patients <40 y.o. than in those >40 y.o. while cancer was absent in patients <40 y.o. However, in patients with FVL and/or FII mutation, acute VTE was more frequently observed after 40 years of age than in patients with AT, PC and PS deficiency, suggesting that all thrombophilias are not the same. The usefulness of screening patients for congenital thrombophilia is suggested in view of its high prevalence. PO-74 Hypercoagulability in multiple myeloma A.D. Petropoulou1 *, G.T. Gerotziafas2 , E. Verdy2 , F. Rendu3 , M.M. Samama1 , M. Hatmi1 , I. Elalamy2 . 1 Service d’H´ ematologie opital Tenon UPMC Paris VI, 3 UMR 7131, Biologique, Hˆ otel-Dieu; 2 Hˆ Hˆ opital Broussais, Paris, France Introduction: We used the Thrombin Generation test (TGT) and measured the plasma levels of soluble thrombomodulin (sTM) to better clarify the multiple myeloma (MM) and thalidomide-related hypercoagulability. Methods: TGT was performed in citrated frozen platelet poor plasma (PPP). Blood was obtained from 22 MM, stage III, patients, 60.8 years old (42 77), 8 treated with thalidomide (T) (200 mg/d) and dexamethasone (D) (40 mg/d for 4 days) (TD group) and 14 receiving no treatment (MM group). 20 healthy volunteers formed the control group. Thrombin Generation (TG) was initiated by adding the PPP reagent (tissue factor and phospholipids) and the triggering solution (CaCl2 and fluorogenic substrate). The analyzed