The Requirement for Viable Platelets in the Coagulation of Heparinized Blood
Activated coagulation times (ACT's) of heparinized blood or plasma samples containing normal platelets were compared with ACT’s of heparinized samples containing non-viable or abnormally functional platelets. The non-viable platelets were prepared by freeze/thawing, and the abnormally functional platelets resulted from the addition of adenosine or adenosine 5'-diphosphate (ADP). The ACT’s of the heparinized samples containing treated platelets were considerably longer than the ACT’s performed on samples with untreated platelets. Treated platelets had no effect on unheparinized samples, however. This would indicate that, although platelet factor 3 (PF3) is sufficient to promote clotting of unheparinized blood, viable platelets, in addition, are required for clotting of heparinized blood. A possible hypothesis which explains these findings is as follows: In the unheparinized situation, coagulation factors are activated as clotting takes place. PF3 serves as a surface catalyst, thrombin is generated, and a fibrin clot is formed. The form in which PF3 is available is incidental to clot formation. When heparin is present, however, thrombin is neutralized as fast as it is formed. Quantities sufficient to induce fibrin formation cannot therefore form in the free plasma, and prolonged or infinite clotting times result. In order for coagulation to go to completion, an environment favorable to thrombin generation must be provided. It is probable that, even in heparinized samples, the foreign surface present and the thrombin formed are sufficient to promote platelet aggregation, even though the thrombin levels are too low to directly affect the coagulation system. The interstices of the platelet aggregates provide an environment favorable to thrombin formation. As the platelets aggregate, plasma containing activated clotting factors and heparin is trapped within the platelet clump. Platelet factor 4 (PF4) is released from the platelets and, in the static environment within the clump, is able to completely neutralize the heparin trapped there. This then allows thrombin generation to proceed catalytically. Fibrin formation can now go to completion, both within the platelet aggregate and in the "plasmatic atmosphere" closely surrounding the clump. The large amounts of thrombin generated overcome the heparin effect, and visible clotting occurs. The implications of an hypothesis such as this may be summarized as follows: 1. Viable platelets are essential to the coagulation of heparinized blood and plasma samples. 2. The varying sensitivities of different individuals to comparable heparin doses may in part reflect the platelet function of those individuals. 3. The fact that variable (and sometimes considerable) numbers of platelets remain in plasma used for activated partial thromboplastin time (APTT) testing implies that the APTT results on such heparinized samples will be correspondingly variable. 4. The APTT, because it is not dependent on the patient's own platelet level, cannot truly reflect that patient's response to heparin. 5. A test such as the activated coagulation time (ACT), which is dependent on the patient's quantitative and qualitative platelet level, reflects more accurately the actual in vivo function of heparin than does the APTT.
Health Information Technology, Blood Coagulation Factors; Blood Platelets.
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