Dendrons and dendrimers are nanoscale polymer molecules with unique hyperbranched structure. The high number of functional groups enable these polymers to be easily modified further, thus creating potential for use as therapeutics. Their interactions with biological systems are mainly predetermined by their chemical structure, terminal groups, surface charge and by the number of branched layers (i.e. generation). Blood compatibility is a mandatory requisite for the safe intravenous administration of drug-loaded nanoparticles. In this work, we assessed the interactions of originally synthesized amphiphilic phosphorous dendrons with whole human blood. We investigated changes in more than dozen hematological and some coagulation parameters upon addition of the first and second generation dendrons at the lower and upper limits of the concentration range (2-10 µM) examined in our previous experiments. We found significantly decreased number of platelets associated with a significant increase in the activated partial thromboplastin time for the combination of higher concentration and the 2^nd generation dendron. Viewing blood films under the light microscope confirmed occasional platelets clumps in this experimental condition. Findings at other conditions were not associated with any clinical significance from a hematological point of view. Our data indicate that thrombogenic propensity might not be the only issue in the nanomedicine safety. Coagulation abnormalities may also relate to prolonged clotting time – presumably as a result of induced consumption of clotting factors and/or platelets. In vitro assays using human blood appear to be a suitable tool to study mechanisms of dendron-based nanomedicines interference with hemostasis and to optimize their hemocompatibility.