Coagulation Abnormalities Produced by Plasma Exchange on the Cell Separator with Special Reference to Fibrinogen and Platelet Levels

Abstract

Five patients with immunopathologic renal disease, 12 with malignant paraproteinaemia and one with myasthenia gravis underwent a total of 179 plasma exchanges on a continuous flow cell separator. Replacement fluids devoid of coagulation factors were used in 160 exchanges while 19 exchanges were replaced with Fresh Frozen Plasma. Coagulation screening was done immediately before and 30 min after each plasma exchange. Plasma fibrinogen concentrations fell to a mean of 25% of initial levels during individual exchanges. Sequential reduction to 10.7% was observed after five consecutive daily exchanges and in one patient fell to 1.2% after 10 daily exchanges. Low levels of fibrinogen could be maintained with daily or alternate daily exchanges. Platelet counts fell to a mean of 50% of pre-exchange levels during individual exchanges. Consecutive daily exchanges resulted in mean reductions to 20.7% after 5 d, but further reductions were not observed with longer periods of exchange. Platelet counts recovered to pre-exchange values during exchange intervals of 2 or more days. Mild clinical bleeding episodes, probably related to low platelet counts, occurred in one exchange in each of three patients. Haemostasis was rapidly achieved in these patients by infusions of platelet concentrates. Coagulation screening, including prothrombin ratio, thrombin time, reptilase time and partial thromboplastin time with kaolin showed progressively greater abnormalities as the intervals between exchanges shortened. The low incidence of clinical haemorrhagic episodes, three of 179 exchanges (2.2%), despite markedly abnormal coagulation parameters, emphasize the safety of the procedure even in moribund patients. We conclude that the use of FFP in intensive exchange programmes solely for the prevention of spontaneous haemorrhagic phenoma is unjustified.

Fibrinogen Reduction and Bleeding Complications in Plasma Exchange, Immunoadsorption and a Combination of the Two

“…TPE/IAS, performed with lower TPE exchange volume, did not differ significantly with a 58% reduction and a fibrinogen concentration below 100 mg/dl in 17% of treatments, and therefore does not offer the advantage of limiting fibrinogen loss. In accordance with our results, Keller et al reported a mean reduction of 75%, but fibrinogen concentration decreased even to 10.7% of baseline after five consecutive treatments [6], which may explain the exceptionally high rate of hypofibrinogenemia in our collective.…”

“…However, since most of the bleedings were related to invasive procedures or menstruation and since there is no control group, it cannot be concluded that IAS leads to additional bleedings. In concordance with previous studies [6,7], post-treatment fibrinogen concentration did not influence the rate of bleeding, and only one of 62 post-treatment fibrinogen concentrations below 100 mg/dl did result in a bleeding event.…”

“…Proteins and other plasma constituents return to pre-treatment levels at different rates: fibrinogen is reduced the most and recovers the least of all coagulation factors, requiring 48 h to resynthesize half of the pre-treatment level [4,5]. Although a reduction of coagulation parameters does not necessarily increase the risk of bleeding [6,7], hypofibrinogenemia has been reported as a risk factor in pregnancy and surgery [8]. A subgroup of TPE patients with very low post-treatment fibrinogen levels and slow recovery may be exposed to a similar risk for up to three days.…”

Improved survival of patients with homozygous familial hypercholesterolaemia treated with plasma exchange.

“…Plasma exchange also reduces plasma fibrinogen concentrations, platelet counts, and high density lipoprotein cholesterol concentra- tions, but these all return to normal within a week, 30 We thank all our colleagues, both doctors and nurses, whose skill and stamina have enabled well over 1000 plasma exchanges to be undertaken over the past 10 years without mishap, Drs J Goldstein and M Brown for measuring the low density lipoprotein receptor state of fibroblasts from the three patients treated in Britain, and Dr R Peto and Mr D Robinson for undertaking the statistical analysis.…”

Selective Fibrinogen Apheresis for Improvement in Microvascular Hemodynamics

“…When multiple treatments are performed over a short period (i.e. three or more treatments per week), the depletion is more pronounced and may require several days for spontaneous recovery [2][3][4][5] . Thus, given the relatively short half-life of fibrinogen (approximately 4 days), it would appear that maintaining a time-averaged reduction in the plasma fibrinogen level, and, in so doing, maintaining the beneficial effects on the microvascular circulation, one would have to perform repetitive treatments over a prolonged period of time.…”