Recurrent early filter clotting in regional citrate anticoagulated continuous venovenous hemodialysis due to undetected antibodies to heparin-platelet factor 4 complexes

Introduction

We recently published a citrate anticoagulated continuous venovenous hemodialysis (citrate-CVVHD) protocol with variable treatment dose. The protocol was safe and easy to handle and the mean filter lifetime was 61.5 hours [1]. We here report five cases with unexplained recurrent early filter clotting beside effective citrate anticoagulation due to undetected antibodies to heparin-platelet factor 4 complexes (hep-PF4 ab).

Methods

Regionale citrate anticoagulation was performed with variable treatment dose using the MultiFiltrate™ CRRT device (Fresenius, Germany) in CVVHD mode. Between May 2008 and August 2009 we detected five cases on the ICU. All had acute kidney injury with need for RRT. Underlying diseases were: three sepsis, one cardiac surgery, one abdominal surgery. All patients were anticoagulated with heparin or fractionated heparin for more than 10 days before initiation of citrate-CVVHD. At the time of initiation of citrate-CVVHD, none of the patients had clinically evident signs of thomboembolism.

Results

The mean filter lifetime before diagnosis of hep-PF4 ab was 8 (range 1.3 to 14) hours. Postfilter ionized calcium concentrations were always in the demanded range (mean 0.28, range 0.24 to 0.35 mmol/l). The mean thrombocyte count was 160/nl (range 48 to 215) at time of initiation of citrate-CVVHD. Thrombocyte counts fell to a mean 114/nl (range 36 to 177) within 5 days. Mean time to testing for and diagnosis of hep-PF4 ab was 6 (range 3 to 12) days. After positive testing (HIPA) for hep-PF4 ab, heparin was stopped and all patients received argatroban with a mean PTT of 83 (range 48 to 119) seconds. Under systemic anticoagulation with argatroban, the filter lifetime of citrate-CVVHD increased to a mean 58 (range 18 to 96) hours. Within 14 days after initiation of citrate-CVVHD, three patients had a diagnosis of a clinically significant thrombembolic event.

Conclusions

In patients on the ICU with moderate-low thrombocyte count and without clinically evident signs of thomboembolism, often sepsis or the state of critical illness is assumed as the cause for decreasing platelet counts and tests for hep-PF4 ab are not performed. In cases of undetected and untreated hep-PF4 ab, filter clotting can occur beside effective citrate anticoagulation in CVVHD. In cases of unexplained recurrent early filter clotting in citrate-CVVHD, patients should be carefully examined for underlying hep-PF4 ab and heparin-induced thrombocytopenia.