Disorders of hemostatic system in patients with malignant disease, especially in view of venous thromboembolism

2007 ◽  
Vol 148 (36) ◽  
pp. 1691-1697 ◽  
Author(s):  
Géza Bozóky ◽  
Éva Ruby ◽  
Ilona Góhér ◽  
Andrea Mohos ◽  
Csilla Bálint ◽  
...  

A szolid malignus kórképekben laboratóriumi módszerekkel igazolható fokozott trombózishajlam a daganatsejtek haemostasisrendszerre gyakorolt aktiváló hatása következtében alakul ki. Az aktiváló hatás a daganatsejtek és a koagulációs rendszer különböző alkotóelemei (véralvadási faktorok, thrombocyták, endothel, fibrinolitikus rendszer) közötti interakció révén alakul ki, s ez vezet a protrombotikus állapottól a haemostasisrendszer klinikailag megnyilvánuló zavaraihoz. Célkitűzés: Retrospektív analízis során a szerzők arra kerestek választ, hogy nagy esetszámú szolid malignus daganatos betegben milyen jellegű és gyakoriságú haemostaticus rendellenességek fordulnak elő. Módszer: Az 1996 és 2004 közötti időszakban 1381 betegben hisztológiai és/vagy citológiai vizsgálat révén kórisméztek szolid malignus megbetegedést. A betegek többsége primer bronchopulmonalis kiindulású karcinómában szenvedett ( n = 1140). A többi esetben emlő-, colorectalis, vese-, húgyhólyag-, pajzsmirigy- és pancreaslokalizációjú volt a malignus folyamat, mesotheliomát hat betegben kórisméztek. A stádiummegállapító vizsgálatok alapján a betegek nagyobb hányada előrehaladott klinikai stádiumú volt. A daganatos betegekben azt vizsgálták, hogy milyen jellegű és gyakoriságú haemostaticus rendellenesség fordul elő, különös tekintettel a vénás thromboemboliák előfordulására. Külön is figyelmet fordítottak a meglevő nem malignus társbetegség szerepére a haemostaticus rendellenességek kialakulása szempontjából. Eredmények: Az 1381 rosszindulatú daganatos betegben 397 esetben (28,7%) észleltek klinikailag megnyilvánuló haemostaticus rendellenességet. Leggyakoribbnak a mélyvénás trombózis és akut pulmonalis embólia bizonyult ( n = 305, 22%). Egyéb jellegű haemostasiszavar (migráló felületes thrombophlebitis, szeptikus trombózis, akut diffúz intravascularis coagulatio, microangiopathiás haemoliticus anaemia) 71 betegben fordult elő, amely 6,7%-nak felel meg. A haemostaticus eltéréssel járó malignus kóresetek 40%-ában nem malignus társbetegséget észleltek, különböző cardialis megbetegedések, valamint a krónikus obstruktív tüdőbetegség dominanciájával. A fokozott trombóziskészséget kiváltó szisztémás okok mellett közel 10%-os gyakoriságban a jelentős nagyságú lokoregionális tumorvolumen is hozzájárult a vénás keringési zavar kialakulásához. Következtetések: Szolid malignus betegekben a daganatsejtek és a koagulációs szisztéma egyes alkotóelemei közötti interakció fokozott trombózishajlam kialakulásához vezet, melynek következtében különböző klinikai megjelenésű haemostasis-rendellenességek jelentkezhetnek. Ezen haemostasiszavarok közül a klinikai gyakorlatban leggyakrabban a vénás thromboemboliák fordulnak elő. Idiopátiás vénás trombózisok eseteiben célzott vizsgálatok elvégzése indokolt az aszimptomatikus (okkult) malignus betegség igazolása, illetőleg kizárása céljából.

1997 ◽  
Vol 78 (05) ◽  
pp. 1327-1331 ◽  
Author(s):  
Paul A Kyrle ◽  
Andreas Stümpflen ◽  
Mirko Hirschl ◽  
Christine Bialonczyk ◽  
Kurt Herkner ◽  
...  

SummaryIncreased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment Fl+2 (Fl+2) was determined in the patient’s plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher Fl+2 levels than patients without H-HC (mean 0.52 ± 0.49 nmol/1, median 0.4, range 0.2-2.8, versus 0.36 ± 0.2 nmol/1, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3,6,9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher Fl+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either Fl+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated Fl+2 level(s) followed by recurrent VTE. No statistical significant difference in the Fl+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.


1999 ◽  
Vol 82 (10) ◽  
pp. 1222-1226 ◽  
Author(s):  
W. Åberg ◽  
D. Lockner ◽  
C. Paul ◽  
M. Holmström

SummaryThe primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i. v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the post-thrombotic score was significantly higher among patients with initial proximal DVT (p = 0,0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29,4% of the patients treated with dalteparin and in 23,5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40,7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.


2009 ◽  
Vol 27 (29) ◽  
pp. 4881-4884 ◽  
Author(s):  
Ajay K. Kakkar

Venous thromboembolism is a common complication in patients with malignant disease. One of the environments in which patients can present with symptomatic thromboembolic disease is in the postoperative period. Operation in the patient with cancer increases the risk of thromboembolic complications some two to three fold. A variety of methods have been evaluated for the prevention of thromboembolic disease in cancer surgical patients. The most extensively investigated are the pharmacologic methods, including low-dose unfractionated heparin and low molecular weight heparin. These agents are recommended for the prevention of thromboembolic disease during hospital stay. For selected high-risk populations, extended thromboprophylaxis into the postdischarge period is also recommended.


1999 ◽  
Vol 82 (10) ◽  
pp. 1232-1236 ◽  
Author(s):  
Ansgar Weltermann ◽  
Karl Philipp ◽  
Erich Hafner ◽  
Alexandra Kaider ◽  
Eva-Maria Kittl ◽  
...  

SummaryNormal pregnancy is associated with alterations of the hemostatic system towards a hypercoagulable state and an increased risk of venous thromboembolism. The risk of venous thrombosis is higher in pregnant women with factor V Leiden (FVL) than in those with wildtype factor V. Routine laboratory assays are not useful to detect hypercoagulable conditions. A prospective and systematic evaluation of hemostatic system activation in women with and without FVL during an uncomplicated pregnancy employing more sensitive markers of hypercoagulability, such as prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential (ETP), an indicator of the plasma’s potential to generate thrombin, has not been performed. We prospectively followed 113 pregnant women with (n = 11) and without (n = 102) FVL and measured F1+2, TAT, D-Dimer and the ETP at the 12th, 22nd and 34th gestational week as well as 3 months after delivery (baseline) in each subject. None of the women developed clinical signs of venous thromboembolism during pregnancy or postpartum. Pregnant women with and without FVL exhibited substantial activation of the coagulation and fibrinolytic system as indicated by a gradual increase of F1+2, TAT and D-Dimer throughout uncomplicated pregnancy up to levels similar to those found in acute thromboembolic events (p < 0.0001 by analysis of variance for each parameters). Levels of F1+2 and TAT were comparable between women with and without FVL, but levels of D-Dimer were significantly higher in women with FVL than in those without the mutation (p = 0.0005). The ETP remained unchanged in both women with and without FVL at all timepoints. Our data demonstrate a substantial coagulation and fibrinolytic system activation in healthy women with and without FVL during uncomplicated pregnancy. An elevated F1+2, TAT or D-Dimer level during pregnancy is not necessarily indicative for an acute thromboembolic event. The normal ETP in both women with and without FVL suggests that the capacity of the plasma to generate thrombin after in vitro activation of the clotting system is not affected by pregnancy. Higher levels of D-Dimer in women with FVL than in women with wildtype factor V at baseline as well as during pregnancy indicate increased fibrinolytic system activation in carriers of the mutation.


Author(s):  
Gary H. Lyman ◽  
Alok A. Khorana ◽  
Anna Falanga

The American Society of Clinical Oncology (ASCO) recently updated clinical practice guidelines on the treatment and prevention of venous thromboembolism (VTE) in patients with cancer. Although several new studies have been reported, many questions remain about the close relationship between VTE and malignant disease. The risk of VTE among patients with cancer continues to increase and is clearly linked to patient-, disease- and treatment-specific factors. In general, VTE among patients with cancer is treated in a similar fashion to that in other patient populations. However, the greater risk of VTE in patients with cancer, the multitude of risk factors, and the greater risk of VTE recurrence and mortality among patients with cancer pose important challenges for surgeons, oncologists, and other providers.


2004 ◽  
Vol 26 (12) ◽  
pp. 1091-1094
Author(s):  
Michelle Susanne Suga Rak ◽  
Mary-Frances Scully

1987 ◽  
Author(s):  
M Levine ◽  
A Arnold ◽  
L Kelleher ◽  
S Lord ◽  
W Hryniuk ◽  
...  

Malignant disease is recognized as a risk factor for venous thromboembolism. A number of recent reports have suggested that cancer chemotherapy may contribute to this risk, but it was not possible to separate the role of chemotherapy from the effects of the malignant disease. We are conducting a randomized trial to determine the optimal duration of adjuvant chemotherapy in women with Stage II breast carcinoma. These ambulatory patients, with negligible tumour burden, receive either 12 weeks of chemo-hormonal therapy (cyclophosphamide, methotrexate, 5 fluorouracil, vincristine, prednisone, adriamycin and tamoxifen) or 36 weeks of chemotherapy (cyclophosphamide, methotrexate, 5 fluorouracil, vincristine and prednisone). This study has provided us with an opportunity to evaluate the thrombogenic effects of chemotherapy since patients in the 12 week group, while off chemotherapy, can be compared directly to the patients in the other group who are still on chemotherapy. This allows the confounding influence of the malignant process to be circumvented. All patients undergo screening tests for thrombosis (impedance plethysmography and Doppler ultrasound) and routine clinical assessments. Suspected venous thrombosis is confirmed by venography and suspected pulmonary embolism by either pulmonary angiography or high probability ventilation perfusion scanning. There have been 11 episodes of venous thromboembolism to date among 191 patients of whom 164 have completed the first 36 weeks of study. There were 3 episodes in each group during the first 12 weeks. During the subsequent 24 weeks there have been no events in the group whose treatment was stopped and 5 events in the group still on treatment (p 0.03). These findings demonstrate that chemotherapy per se is an important risk factor for venous thromboembolism in patients with malignant disease.


1998 ◽  
Vol 28 (5) ◽  
pp. 800-807 ◽  
Author(s):  
Daniel M. Ihnat ◽  
Joseph L. Mills ◽  
John D. Hughes ◽  
Andrew T. Gentile ◽  
Scott S. Berman ◽  
...  

VASA ◽  
2014 ◽  
Vol 43 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Thomas Gary

Cancer is a highly thrombophilic entity leading to a high rate of symptomatic and even asymptomatic venous thromboembolic (VTE) events in patients suffering from malignant disease. As VTE events have impact on survival and can be reduced significantly by anticoagulant treatment, guidelines on prophylaxis of these events by means of anticoagulation exist from various societies. Purpose of this review is to give a concise overview of current possibilities for prophylaxis and also for the therapy of VTE events in cancer patients.


Sign in / Sign up

Export Citation Format

Share Document