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Hamostaseologie 2019; 39(01): 006-019
DOI: 10.1055/s-0038-1676823
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Microvascular Thrombosis and Ischaemic Limb Losses in Critically Ill Patients

Theodore E. Warkentin
1   Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
2   Transfusion Medicine, Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
3   Service of Clinical Hematology, Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada
4   McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada
5   Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations
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Publication History

20 September 2018

02 November 2018

Publication Date:
09 January 2019 (online)

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Abstract

Relatively little scientific attention has been given to the small subset of critically ill patients with circulatory shock who develop ischaemic limb losses (symmetrical peripheral gangrene [SPG]). The clinical picture consists of acral (distal extremity) tissue necrosis involving lower limbs in a largely symmetrical fashion and with detectable arterial pulses; in one-third of patients the upper extremities are also affected (potential for four-limb amputations). The laboratory picture includes thrombocytopenia, coagulopathy, and normoblastemia (circulating nucleated red blood cells). The explanation for limb losses is microvascular thrombosis caused by disseminated intravascular coagulation usually secondary to cardiogenic or septic shock. A common myth is that vasopressors cause the ischaemic limb injury. However, the more likely explanation is failure of the natural anticoagulant systems (protein C and antithrombin) to downregulate thrombin generation in the microvasculature. This is because more than 90% of patients with SPG have preceding ‘shock liver’, which occurs 2 to 5 days (median, 3 days) prior to ischaemic limb injury, with impaired hepatic production of protein C and antithrombin.

Zusammenfassung

Die kleine Gruppe kritisch kranker Patienten mit Herz-Kreislauf-Schock und ischämisch bedingter Extremitäten-Gangrän hat bislang relativ wenig wissenschaftliche Aufmerksamkeit erfahren. Das klinische Bild besteht aus ischämischen Gewebsnekrosen der Akren trotz nachweisbarem arteriellen Puls. Die Nekrosen treten typischerweise symmetrisch und vor allem an den unteren Extremitäten auf. Bei ca. einem Drittel der Patienten sind auch die Finger/Hände betroffen (Risiko der Amputation aller vier Extremitäten). Die Laborergebnisse zeigen die Konstellation von Thrombozytopenie, Koagulopathie und zirkulierenden Normoblasten (kernhaltigen Erythrozyten). Der Extremitätenverlust wird verursacht durch mikrovaskuläre Thrombosen bei disseminierter Koagulopathie infolge eines kardiogenen oder septischen Schocks. Ein weit verbreiteter Irrglaube ist, dass Vasopressoren eine Ischämie der Akren/Extremitäten verursachen. Die viel wahrscheinlichere Erklärung dürfte sein, dass ein Versagen der natürlichen antikoagulatorischen Systeme (Protein C, Antithrombin) aufgrund einer Leberschädigung dazu führt, dass die Thrombinbildung in der Mikrozirkulation nicht ausreichend gehemmt wird. Mehr als 90% der Patienten mit symmetrischer Extremitäten-Gangrän haben eine ‘Schockleber’, die 2–5 Tage (im Median 3 Tage) vor Entstehung der Extremitäten-Gangrän auftritt und zu mit eingeschränkter Synthese von Protein C und Antithrombin führt.

Keywords

acute ischaemic hepatitis (‘shock liver’) - antithrombin - disseminated intravascular coagulation - protein C - symmetrical peripheral gangrene - vasopressors

Schlüsselwörter

akute ischämisce Hepatitis (‘Schockleber’) - Antithrombin - Disseminierte intravaskuläre Koagulation - Protein C - Symmetrisches peripheres Gangrän - Vasopressoren
 

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