The fifth INTERMACS annual report, comparing the adverse event rate of pulsatile and continuous-flow VAD technology, demonstrated a significantly lower risk of bleeding and thrombotic events in patients treated with the newer-generation continuous-flow VADs [4].

This decreased risk of thrombotic and hemorrhagic events has been one of the drivers behind the marked increase in the use of continuous-flow devices in recent times. However, continuous devices are not a homogenous group, as they include both axial-flow and centrifugal-flow pumps, which differ significantly in their characteristics and would be expected to have different effects on the coagulation and hematological systems [5].

Indeed, patients with HeartWare HVAD^®, a centrifugal-flow pump, show higher levels of D-dimer, MCF in ROTEM tests, platelet count, and activation at the aggregometer. On the other hand, axial-flow pumps, namely, Thoratec HeartMate II^® and Jarvik 2000 FlowMaker^®, are associated with signs of hemolysis, as suggested by elevated LDH [6, 7].

Beyond the theoretical interest in understanding the effects of various VAD designs on the coagulation and hematological systems, there is also significant potential for clinical application of this knowledge.

For example, in 2011 HeartWare noticed an unexpectedly high rate of pump thrombosis, which was associated with subtherapeutic INR and low aspirin dose (81 mg or less). The implementation of a stricter INR protocol, together with ASA adjustment to 325 mg, resulted in a drop of pump exchange and ischemic strokes. Interestingly, the more aggressive antithrombotic treatment was not associated with higher incidence of bleeding or hemorrhagic strokes [8].

However, these results were also due to technical improvements, as the introduction of an enhanced coring tool and sintered inflow cannula. Yet another example of a specific VAD model enhancement having a clinical impact is the one of Jarvik 2000, where the shift of the bearing mechanism from pin to cone design resulted in improved survival and reduced incidence of stroke [9].

Lastly, in the USA, an abrupt increase in pump thrombosis was also observed with HeartMate II, starting in mid-2011 [10]. The precise causes still remain unknown, but it has been hypothesized that the level of anticoagulation was insufficient.

According to the aforementioned findings, it is possible to outline a rational antithrombotic therapy from the outset. In fact, HeartWare patients are usually treated with both anticoagulant and antiplatelet drugs, and HeartMate II alike, while Jarvik patients are kept only on anticoagulation.

Another factor to bear in mind is that the patient’s coagulation system, and subsequently its interaction with the VAD, changes over time. This occurs either per se, and following several physiological and pathological processes, which are not always evident or predictable. Examples include infections, hemorrhages, right ventricular failure, and other medications.

As a result, it is essential to constantly monitor coagulation with both quantitative and qualitative tests and tailor the antithrombotic therapy accordingly.

Generally, MCS patients are treated with a modified version of the multitargeted antithrombotic approach (MTA) originally proposed for total artificial heart management [11]. Protocols consist of anticoagulation with unfractionated heparin and warfarin, eventually bridged with fondaparinux, and antiplatelet therapy with aspirin, and clopidogrel when appropriate.

MTA is best calibrated with a multimonitoring system (MMS) using conventional laboratory markers such as complete blood count, prothrombin time, aPTT, D-dimer, and fibrinogen and ATIII levels, together with thromboelastometry and aggregometry.

Rotational thromboelastometry (ROTEM^®, Tem International GmbH, München, Germany) is a whole blood coagulation method that provides information about clot strength and stability and indirectly about platelet function. The clot forming in an oscillating cuvette transmits its movement onto a suspended piston, which is recorded continuously and given a graphic representation [12]. Various tests, performed with specific reagents, allow to evaluate the different contributions to coagulation cascade: Intem^® activates the contact phase of hemostasis, evaluating intrinsic pathway; Extem^® screens extrinsic pathway via tissue factor activation; and Fibtem^® eliminates platelet contribution, allowing evaluation of fibrinogen activity. Briefly, the measured parameters are clotting time (CT), which is the time until initiation of clotting, affected by coagulation factors; clot formation time (CFT), which is the time from CT until a clot firmness of 20 mm is reached; and maximum clot firmness (MCF), which is the greatest amplitude reached by the clot. Both CFT and MCF correlate with platelet number and function, fibrin polymerization disorders, and fibrinogen function, but MCF is usually considered in that it best describes the clot quality.

Platelet aggregation can be measured with the Multiplate^® analyzer (Roche Diagnostics, Mannheim, Germany), a whole-blood impedance aggregometer (which measures the change of resistance between two platinum electrodes, proportional to the amount of platelets attached to them) [13]. Again, several tests are available to evaluate platelet aggregation induced by different agonists: