do czstych powika mcs nale : incydenty zakrzepowe ( w tym zakrzepica urzdzenia ) , incydenty krwotoczne oraz hemoliza .
ocena zmian w czasie wybranych parametrw ukadu krzepnicia u chorych ze schykow niewydolnoci serca leczonych za pomoc mcs i terapii przeciwzakrzepowej .
przez 6 tygodni obserwowano 16 pacjentw ze schykow niewydolnoci serca ( sze pobra krwi dla kadego pacjenta ) .
co tydzie oceniano rozszerzony panel bada ukadu krzepnicia , w tym czas czciowej tromboplastyny po aktywacji , czas protrombinowy , midzynarodowy wspczynnik znormalizowany , aktywno czynnika von willebranda ( vwf ) , aktywno czynnika viii , stenie fibrynogenu , d - dimeru , czynno pytek pod wpywem kwasu arachidonowego ( aspi test ) i dwufosforanu adenozyny ( adp test ) , aktywujcego receptora trombinowego peptydu 6 ( trap test ) i kolagenu ( col test ) .
mediana czasu od momentu wszczepienia urzdzenia wspomagajcego prac lewej komory serca ( lvad ) wynosia 120 dni ( 100150 dni ) .
podczas badania stenia d - dimeru oraz fibrynogenu byy podwyszone we wszystkich szeciu oznaczeniach , nie stwierdzono istotnych rnic midzy kolejnymi oznaczeniami .
aktywno vwf i czynnika viii byy podwyszone w pierwszych dwch oznaczeniach , w kolejnych oznaczeniach obserwowano ich zmniejszenie .
u pacjentw stosujcych mcs wykazano znaczne zmiany w parametrach hemostazy zarwno w ukadzie krzepnicia , jak i aktywnoci pytek krwi .
heart transplantation remains the first - line therapy in the management of end - stage heart failure .
however , the number of transplants is estimated at less than 3,500 yearly worldwide , which is obviously inadequate to meet the demand in this rapidly growing population of heart failure patients [ 1 , 2 ] . mechanical circulatory support ( mcs )
is an umbrella term describing various technologies used in both short- and long - term management of patients with either end - stage chronic heart failure ( hf ) or acute hf .
bridge to transplant to support patients who are unable to wait any longer for a heart transplant , or , more recently , as  destination therapy for older patients suffering from end - stage heart failure and who have contraindications to heart transplantation [ 3 , 4 ] .
mechanical circulatory support includes a left ventricular assist device ( lvad ) or a bi - ventricular assist device ( bi - vad ) . however , mcs therapy is not without risk .
recently , clinicians have identified common mcs therapy - associated complications : pump thrombosis , bleeding , and hemolysis .
the incidence of lvad thrombosis is 213% of adult patients with a continuous - flow lvad ( axial flow 413% , centrifugal flow 2% ) .
therapeutic options include surgical procedures ( device exchange , catheter - based thrombectomy ) and medical therapy .
the latter may consist of : thrombolytic therapy with recombinant tissue plasminogen activator , intensified anticoagulation treatment with unfractionated heparin , bivalirudin , intensified antiplatelet treatment with intravenous gp iib / iiia inhibitors , or with thienopyridine - derivative p2y12 adp receptor inhibitor . however , there are no unified guidelines as to the antithrombotic therapy [ 7 , 8 ] .
the incidence of lvad - associated bleeding , depending on its definition , varies widely between 10% and 50% , with no difference in the overall bleeding rates between axial- and pulsatile - flow devices .
much of the bleeding risk is attributed to the antithrombotic regimen . however , there are reports that the observed increased risk of bleeding is higher than would be anticipated from antithrombotic therapy alone . given the coexistence of thrombo - embolic and hemorrhagic complications , monitoring of hemostasis using thromboelastometry/-graphy and platelet function analysis
hemostasis assays should be used to reduce the risk of bleeding and thrombo - embolic complications during mcs therapy and antithrombotic management .
therefore , we set out to determine time - dependant changes of selected hemostasis parameters in patients with end - stage heart failure treated with mcs and antithrombotic therapy .
the study was approved by the local bioethics committee , and all patients gave written consent to participate in the study .
sixteen patients with end - stage heart failure on lvad were followed for 6 weeks ( six blood samples for each patient ) . given the various effects of continuous - flow lvad and pulsatile - flow lvad on hemostasis , we included in the current study only continuous - flow lvad recipients .
the pump is driven by a rotating magnetic levitated impeller and has a capacity of up to 15,000 rpm , resulting in a theoretical maximal blood flow of 810 l / min .
it is a rotational pump with a magnetic levitating rotor ( similar to a propeller ) .
the blood flow is not axial , because inflow and outflow axes are arranged in a 90 degrees angle .
moreover , this pump runs with a lower rotation speed of 1,000 to 2,500 rpm and generates up to 10 l / min flow .
every week an extended hemostasis panel was assessed , including activated partial thromboplastin time ( aptt ) , prothrombin time ( pt ) , international normalized ratio ( inr ) , von willebrand factor ( vwf ) activity , factor viii activity , fibrinogen level , d - dimer , platelet response to arachidonic acid ( aspi test ) and adenosine diphosphate ( adp test ) , thrombin receptor activating peptide-6 ( trap test ) and collagen ( col test ) .
fasting venous blood samples were taken each week , and all tests were performed within one hour of blood samples collection .
whole venous blood samples were collected from each patient and placed in 2 tubes of 4 ml with 109 mmol of sodium citrate ( 3.2% ) and in 2 tubes of 3 ml with > 15 g / ml of hirudin .
plasma was separated by centrifugation at 2000 g for 15 min at ambient temperature ( 2025c ) .
the vwf activity and d - dimers were evaluated by an immuno - turbidimetric assay , using a fully automated hemostasis analyzer ( bcs xp system , innovance siemens healthcare , usa ) .
factor viii ( % activity of normal plasma ) and coagulant fibrinogen ( mg / dl ) were determined by chronometric techniques by means of fully automated hemostasis analyzers ( bcs xp system , siemens healthcare , usa ) .
prothrombin time ( pt , % time of normal plasma ) , inr , and aptt ( s ) were also assessed by chronometric techniques .
platelet aggregation was tested in physiological calcium conditions by the multiplate analyzer ( dynabyte , munich , germany ) , using agonists of thrombin receptor activating peptide-6 ( trap-6 ) , arachidonic acid ( aspi ) , adenosine diphosphate ( adp ) , and a collagen binding activity assay ( col ) .
the antithrombotic protocol involved the use of unfractionated heparin according to the aptt ( 6080 s ) starting on postoperative day ( pod ) 1 . on pod 2 warfarin was started to achieve inr of 2.02.5 in continuous - flow pumps .
in addition , aspirin and/or clopidogrel were used antiplatelet agents , starting from pod 2 .
the type and dose of antithrombotic regimen were at the discretion of the attending physician .
friedman analysis of variance ( anova ) test followed by bonferroni correction and the wilcoxon matched - pairs signed - ranks test were employed to test the difference between repeated laboratory tests during 6-week follow - up .
friedman analysis of variance ( anova ) test followed by bonferroni correction and the wilcoxon matched - pairs signed - ranks test were employed to test the difference between repeated laboratory tests during 6-week follow - up .
baseline clinical characteristic are presented in table i. the study population comprised 16 men with a median age of 41 ( interquartile range : 2449 ) .
the d - dimer and fibrinogen concentrations were elevated but remained similar throughout all six measurements .
meanwhile factor viii and vwf activities were elevated in the first two measurements and then subsequently declined .
baseline clinical characteristics coagulation assay results in studied patients time - dependant changes in platelet function
we set out to determine time - dependant patterns in hemostasis parameters in patients with end - stage heart failure treated with lvad .
first , d - dimer and fibrinogen concentrations were elevated but remained similar throughout all six measurements .
second , factor viii and vwf concentrations were elevated at the beginning of the study and then steadily declined .
finally , despite the fluctuation in hemostasis parameters , there were no hemorrhagic or thrombo - embolic events during the study period .
currently , long - term survival in carefully selected patients on mcs is much better than with medical therapy .
however , mcs therapy is hampered by , sometimes life - threatening , complications including bleeding and device thrombosis .
left ventricular assist device thrombosis etiology is multifactorial and thus presents complex and challenging problems in the diagnosis and management of such patients .
the conditions associated with lvad thrombosis are divided into three large groups : ( a ) pump - related , ( b ) patient - related , and ( c ) management - related . left ventricular assist device thrombosis occurs in 213% of adult patients with a continuous - flow lvad ( axial - flow : 413% , centrifugal - flow : 2% ) .
thrombus may be formed at various sites , i.e. left ventricle , inflow cannula , pump housing , outflow cannula , outflow graft , or the aortic root , thus leading to serious cardiovascular events including thromboembolic stroke , peripheral thromboembolism , lvad malfunction with reduced systemic flows or life - threatening hemodynamic impairment , cardiogenic shock , and even death [ 6 , 15 ] .
the four clinical signs of lvad thrombosis recognized are as follows : ( a ) isolated power elevations , ( b ) isolated ldh rise , ( c ) evidence of hemolysis , and ( d ) new heart failure symptoms .
the multidisciplinary and multi - institutional ishlt group proposed an algorithm for the diagnosis and management of lvad thrombosis .
left ventricular assist device patients experience significant baseline activation of endothelial and coagulation systems , further accentuated in the early postoperative period .
more importantly , prolonged activation of the endothelial and coagulation systems was also reported , which may indicate activation of the extrinsic ( tissue factor ) pathway of thrombosis mediated by sustained endothelial dysfunction in these patients .
elevated d - dimer concentrations , as found in our study , may reflect chronic , ongoing activation of the coagulation system .
elevated concentrations of fibrinogen , factor viii , and vwf might result in a hypercoagulable state resulting in lvad thrombosis .
more importantly , we have to keep in mind that factor viii is an acute - phase protein ( malignancy , chronic diseases , infections ) .
thus , genetic or acquired conditions determining high factor levels might predispose patients to lvad thrombosis .
the vwf has a pivotal role in thrombogenesis , and high plasma levels of vwf have been associated with increased risk of thrombosis . a varied response to the antiplatelet regimen , as demonstrated during the study period ,
one study found that asa doses at or below 81 mg / day were an independent predictor of device thrombosis .
reported that pump thrombosis was preceded by an almost surprising increase in platelet aggregation induced by aspi and adp .
thus the authors argue that an increase of platelet reactivity or non - response ( or low response ) to antiplatelet therapy may , in part , play a role in pump thrombosis .
indeed , elevated expression of platelet membrane receptors , namely cd62p and cd63 , have been reported in patients on lvad .
left ventricular assist device thrombosis has been reported in non - responders to aspirin   and clopidogrel .
in addition to thrombosis , bleeding has recently been identified as one of the most common adverse events of lvad therapy and is the major cause of morbidity .
having said that , some authors report that the increased risk of bleeding is higher than would be attributed to antithrombotic therapy .
the most commonly reported sources of bleeding are epistaxis , gi bleeding , bleeding of the mediastinum and thorax , and intracranial hemorrhage .
the incidence of bleeding , depending on its definition , varies widely between 10% and 50% , with no difference in the overall bleeding rates between axial- and pulsatile - flow devices .
the mechanisms underlying bleeding in lvad patients are complex and not yet fully understood , and include colonic dysplasia , concomitant use of anticoagulant and antiplatelet agents , and the presence of acquired bleeding diathesis ( acquired von willebrand syndrome type 2a resulting from the deficiency of high - molecular - weight vwf multimers ) . as such
, high - molecular - weight vwf multimers declined in patients with lvad [ 27 , 28 ] , but returned to normal in 6 patients after heart transplantation .
however , in the present study we measured only vwf antigen , which is generally within the normal range or elevated and can not be used in the confirmation or exclusion of acquired von willebrand syndrome type 2a .
the sensitivity of various laboratory tests for vws2a in patients with bleeding gi dysplasia is as follows : gel electrophoresis ( quantification of hmwm ) > pfa-100 closure time > vwf : rco > bleeding time > vwf : ag [ 15 , 30 ] .
it would seem that lvad recipients achieve a new equilibrium between prothrombotic and prohemorrhagic states .
more importantly , there is a fine and complex balance in the management of such patients of overcoagulation and undercoagulation .
management protocols for lvad are usually institution - dependent , and unfortunately , there is a large variability in clinician - related factors .
we have to keep in mind that the  one size fits all  approach is impractical and ineffective
. therefore , individually tailored antithrombotic therapy protocols must exist in centers managing lvad recipients .
we did not assess the dysfunction of vwf ( in particular the deficit of high molecular weight multimers of vwf assessed in gel electrophoresis ) .
moreover , we did not use thromboelastographic ( teg ) monitoring , which could have provided additional information , as teg is uniquely capable of showing the combined interaction of coagulation factors , platelet content , and platelet function in the process of clot production in whole blood .
patients with end - stage heart failure on lvad therapy demonstrate significant time - dependant changes in hemostasis parameters that could be attributable to the risk of developing both thrombotic and bleeding events . however , further studies are needed to determine whether these changes could serve as biomarkers of such events .
the creation of the paper was supported by a grant funded by the medical university of silesia ( no .
 introductionmechanical circulatory support ( mcs ) therapy is associated with the improvement of long - term prognosis in patients with end - stage heart failure . for years 
 it has been used as a bridge to transplant . 
 however , more recently it is even being used as a destination therapy . 
 recently , clinicians have identified common mcs therapy - associated complications : pump thrombosis , bleeding , and hemolysis . 
 these complications are very challenging with regard to both diagnosis and management.aimto determine time - dependant changes of selected hemostasis / coagulation parameters in patients with end - stage heart failure treated with mcs and antithrombotic therapy.material and methodssixteen patients with end - stage heart failure on left ventricular assist device ( lvad ) were followed for 6 weeks ( six blood samples for each patient ) . 
 every week an extended hemostasis panel was assessed , including activated partial thromboplastin time , prothrombin time , international normalized ratio , von willebrand factor ( vwf ) activity , factor viii activity , fibrinogen level , d - dimer , platelet response to arachidonic acid ( aspi test ) and adenosine diphosphate ( adp test ) , thrombin receptor activating peptide-6 ( trap test ) and collagen ( col test).resultsthe study population comprised 16 men . 
 the median time from lvad implantation was 120 days ( 100150 days ) . during the study period 
 the d - dimer and fibrinogen concentrations were elevated but remained similar throughout all six measurements . 
 meanwhile factor viii and vwf activities were elevated in the first two measurements and then subsequently declined . 
 inhibition of platelet aggregation was greater early after lvad implantation . during subsequent weeks 
 the inhibition of platelet aggregation was less pronounced . 
 no patient developed any bleeding or thrombo - embolic event during the study period.conclusionspatients on mcs therapy demonstrate significant time - dependant changes in hemostasis parameters ( both in the coagulation system and platelet aggregation ) . 