Aberration of Coagulation Parameters with a Small Dose of Hydroxyethyl Starch in a Patient with Underlying Factor XII Deficiency: A Case Report.
Authors: Scarvelis Dimitrios 
Published: April 2020

Abstract
Background: Hydroxyethyl starch (HES) is a commonly used intravascular volume expander in the peri-operative period. The use of such volume expanders has been demonstrated to cause significant abnormalities of laboratory tests of hemostasis by a number of mechanisms including a reduction of factor VIII activity. In Canada, Pentaspan® is commonly used, and its shorter half life has been reported to cause less coagulation abnormalities than older HES formulations. A recent study has demonstrated that in patients receiving Pentaspan®, a volume of up to 45ml/kg per 24hrs will not cause significant changes to coagulation parameters (Arellano et al. Anaesth Analg2005;100:1846–53). Following is a report of a coagulopathy caused by much lower doses of Pentaspan®.
Case report: A 53 year old male was scheduled to undergo elective aortic valve replacement for severe aortic stenosis. He had no previous history of a bleeding disorder and one week pre-operatively he had normal coagulation parameters with an activated partial thromboplastin time (aPTT) of 33 seconds (normal range 24–36 sec). On the day of surgery, after sternotomy was performed, the patient experienced an allergic reaction to morphine and developed transient hypotension necessitating a small dose of phenylephrine and 500cc of Pentaspan®. The patient recovered, but subsequent to this, the activated clotting time (ACT) was &gt;300sec in the absence of heparin and the aPTT was 68sec. Other coagulation parameters included a thrombin time of 14sec (upper limit normal (ULN) 16sec), a fibrinogen of 3.7g/L and a heparin anti-Xa level of &lt;0.1 U/cc. The patient did not experience clinical bleeding. The case was aborted and further hematological investigated was initiated. Two hours post-operatively, coagulation parameters revealed the following: Factor VIII activity 0.89 U/cc, factor XI 0.78U/cc, Factor XII 0.28 U/cc, aPTT 62sec. The following day, the aPTT was 32sec and subsequent to this the patient was given a small dose (250cc) of Pentaspan®. One hour post-infusion, the aPTT had risen to 88 seconds. Factor levels were repeated two days later, and this time revealed a factor VIII level of 2.08 U/cc, with factor XII, XI and factor IX levels being similar to those on the day of the surgery. The aPTT on this day was normal at 34 seconds.
This case report demonstrates that a small dose of the HES Pentaspan® caused a significant abnormality in the coagulation testing for this patient with underlying factor XII deficiency. It is hypothesized that normally his elevated factor VIII level compensated for the diminished factor XII level, resulting in a normal aPTT, but that after a small dose of Pentaspan®, the factor VIII level decreased sufficiently so the that the underlying factor XII deficiency was unmasked.
Conclusion: An underlying factor deficiency can result in a laboratory coagulopathy (this case with factor XII deficiency) or potentially a clinical coagulopathy when even small doses of Pentaspan® are used.
1 week pre-op Pentaspan 500cc given intra-op ↓ 10 minutes post Pentaspan 2 hours post Pentaspan Post-operative day 1: pre Pentaspan Post-operative day 1: 1 hour post 250cc Pentaspan Post-operative day 3 Factor VIII 0.89 U/cc 2.08 U/cc Factor IX 1.09 U/cc Factor XI 0.78 U/cc 0.86 U/cc Factor XII 0.28 U/cc 0.26 U/cc Apt 33 sec 68 sec 62 sec 32 sec 88 sec 34 sec INR 1.1 1.1 1.1 1.1 1.3 1.2 Fibrinogen 3.7 g/L Thrombin Time 14 sec Heparin anti-Xa level &lt;0.1 U/cc