CLINICAL NEWS
POT-KAST and POT-CAST : Questioning Routine Thromboprophylaxis After Casting or Knee Surgery
The value of prescribing thromboprophylaxis to prevent venous thromboembolism ( VTE ) after knee arthroscopy or casting of the lower leg is debatable , and the risk−benefit ratio has not been well established .
In a study published in the New England Journal of Medicine , Raymond A . van Adrichem , MD , from the Leiden University Medical Center in the Netherlands , and co-authors provided evidence that prophylaxis with low-molecular-weight heparin ( LMWH ) was not effective for preventing symptomatic VTE , compared with placebo , and that it may be unnecessary in these patients .
“ Routine anticoagulant prophylaxis for patients with lower-leg plaster cast or knee arthroscopy is not recommended , as it was found not to be effective ,” co-author Suzanne Cannegieter , MD , PhD , also from Leiden University Medical Center , told ASH Clinical News . “ This large patient population will not need to be exposed to the burden and risks of anticoagulant therapy anymore .”
Dr . van Adrichem and co-authors conducted two parallel , multicenter , randomized , controlled , open-label trials at 10 hospitals in the Netherlands : POT-KAST ( Prevention of Thrombosis After Knee Arthroscopy ) and POT- CAST ( Prevention of Thrombosis After Lower Leg Plaster Cast ).
In each trial , patients were randomized 1:1 to receive LMWH ( nadroparin or dalteparin administered subcutaneously ) or no anticoagulant therapy ( control group ). Patients were excluded if they had a history of VTE , had a contraindication to LMWH , were pregnant , or were receiving anticoagulant therapy for other indications ( although use of antiplatelet drugs was allowed ).
Patients were followed for three months “ because , after this period , the risk of VTE returns to baseline ,” the authors explained . Follow-up consisted of telephone interviews during which patients were asked whether they had undergone examination for a suspected VTE , visited the hospital , and adhered to the treatment program . The patient ’ s general practitioner was contacted for this information if the patient did not respond .
POT-KAST POT-KAST included adult patients ( mean age = 48.5 ± 12.5 years ) who were scheduled to undergo knee arthroscopy for meniscectomy , diagnostic arthroscopy , removal of loose bodies , or other indications . Between May 2012 and January 2016 , 1,543 patients were randomized , of whom 1,451 were included in
Only with FEIBA prophylaxis
Help stop his bleed before it starts
72 % BLEED
A clinical study showed *
28.7 median Annual Bleed Rate ( ABR ) with on-demand treatment 1 , 2 629 bleeding episodes occurred during on-demand treatment 1 , 2
REDUCTION IN MEDIAN ANNUAL
RATE 1
* PROOF study : Phase 3 , prospective , randomized , open-label study for a period of 12 months in 17 patients who received FEIBA prophylaxis ( 85 ± 15 U / kg every other day ) and 19 patients who received FEIBA on-demand ( dosages determined by treating physicians ). 1
7.9 median ABR with prophylaxis treatment 1 , 2 196 bleeding episodes occurred during prophylaxis treatment 1 , 2
Indications for FEIBA [ Anti-Inhibitor Coagulant Complex ]
FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for :
• Control and prevention of bleeding episodes
• Perioperative management
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes .
FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to coagulation factor VIII or coagulation factor IX .
Detailed Important Risk Information for FEIBA
WARNING : THROMBOEMBOLIC EVENTS
• Thromboembolic events have been reported during post-marketing surveillance following infusion of FEIBA , particularly following the administration of high doses and / or in patients with thrombotic risk factors .
• Monitor patients receiving FEIBA for signs and symptoms of thromboembolic events . The use of FEIBA is contraindicated in patients with :
• Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components , including factors of the kinin generating system
• Disseminated intravascular coagulation ( DIC )
• Acute thrombosis or embolism ( including myocardial infarction )
Thromboembolic events ( including venous thrombosis , pulmonary embolism , myocardial infarction , and stroke ) can occur with FEIBA , particularly following the administration of high doses ( above 200 units per kg per day ) and / or in patients with thrombotic risk factors .
Infusion of FEIBA should not exceed a dose of 100 units per kg body weight every 6 hours and daily doses of 200 units per kg body weight . Maximum injection or infusion rate must not the intention-to-treat population : 731 LMWH-treated patients and 720 controls . LMWH was administered once daily for the eight days following arthroscopy , with the first dose administered post-operatively , but before discharge , on the day of surgery .
VTE was suspected in 12 patients and confirmed in five ( 0.7 %) in the treatment group ( 4 cases of deep vein thrombosis [ DVT ] and 1 case of pulmonary embolism [ PE ]), while researchers observed 11 suspected cases and three confirmed cases ( 0.4 %) of VTE ( 2 DVTs and 1 PE ) in the control group . The relative risk ( RR ) for VTE was 1.6 ( 95 % CI 0.4-6.8 ), with an
exceed 2 units per kg of body weight per minute . Monitor patients receiving more than 100 units per kg of body weight of FEIBA for the development of DIC , acute coronary ischemia and signs and symptoms of other thromboembolic events . If clinical signs or symptoms occur , such as chest pain or pressure , shortness of breath , altered consciousness , vision , or speech , limb or abdomen swelling and / or pain , discontinue the infusion and initiate appropriate dianostic and therapeutic measures .
Hypersensitivity and allergic reactions , including severe anaphylactoid reactions , can occur following the infusion of FEIBA . The symptoms include urticaria , angioedema , gastrointestnal manifestations , bronchospasm , and hypotension . These reactions can be severe and systemic ( e . g ., anaphylaxis with urticaria and angioedema , bronchospasm , and circulatory shock ). Other infusion reactions , such as chills , pyrexia , and hypertension have also been reported . If signs and symptoms of severe allergic reactions occur , immediately discontinue administration of FEIBA and provide appropriate supportive care .
Because FEIBA is made from human plasma it may carry a risk of transmitting infectious agents , e . g ., viruses , the variant Creutzfeldt‐Jakob disease ( vCJD ) agent and , theoretically , the Creutzfeldt‐Jakob disease ( CJD ) agent .
The most frequently reported adverse reactions observed in > 5 % of subjects in the prophylaxis trial were anemia , diarrhea , hemarthrosis , hepatitis B surface antibody positive , nausea , and vomiting .
The serious adverse reactions seen with FEIBA are hypersensitivity reactions and thromboembolic events , including stroke , pulmonary embolism and deep vein thrombosis .
Use of antifibrinolytics within approximately 6 to 12 hours after the administration of FEIBA is not recommended .
Please see next page for FEIBA Brief Summary of Prescribing Information . To see the Full Prescribing Information , including Boxed Warning on Thromboembolic Events , go to www . FEIBA . com .
References : 1 . FEIBA Prescribing Information . 2 . Antunes SV , Tangada S , Stasyshyn O , et al . Randomized comparison of prophylaxis and ondemand regimens with FEIBA NF in the treatment of haemophilia A and B with inhibitors . Haemophilia . 2014 ; 20 ( 1 ): 65-72 . © 2017 Shire US Inc ., Lexington , MA 02421 . All rights reserved . 1-800-828-2088 . SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates . Feiba is a registered trademark of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc . S27124 01 / 17
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