To the content
2 . 2022

Heparin-induced thrombocytopenia and COVID-19: simplified rule of diagnosis and treatment algorithm

Abstract

Introduction. Thrombocytopenia significantly increases the risk of complications and mortality during surgical interventions, especially in general surgical, cardiac, traumatological and vascular patients. The causes of it in the postoperative period are more often blood loss, hemodilution, sepsis, as well as the use of heparins. Heparin-induced thrombocytopenia (HIT) has an immunospecific genesis, increases the risk of paradoxical thrombosis and the mortality of hospitalized patients, including COVID‑19 patients.

The spontaneous HIT syndrome is described during vaccination against COVID‑19 and mechanical pneumocompression. The diagnosis of HIT is complicated by the inaccessibility and high cost of the method for determining HIT-antibodies, the complexity and low specificity of the existing Risk Scales (the 4T scale, the HEP scale, the Scale for detecting HIT after coronary artery bypass grafting). The aim of the work was to determine the prevalence of HIT in a multidisciplinary hospital, as well as to improve its diagnosis and treatment through the practical implementation of the original diagnosis rule and the algorithm for managing patients with HIT.

Material and methods. The laboratory database for 2013–2015 of a multidisciplinary hospital with 540 beds with an analysis of cases of severe thrombocytopenia was retrospectively analyzed. Since 2014, hospital doctors have been informed about the original rule and the algorithm for managing patients with HIT. The frequency of cases of suspected HIT and its complications were analyzed in dynamics over 3 years by taking into account the number of such patients in hospital departments, including intensive care units.

Results. Severe thrombocytopenia (<100×109/L) was detected in 5018 blood samples obtained from 950 patients (367 + 288 + 295 respectively, in 2013, 2014 and 2015) out of 75 123 treated during this period, which was 1.3%. 2 groups of patients were identified: patients with suspected HIT (who received heparins) and those who did not receive heparins. The dynamics showed the decrease in the number of severe thrombocytopenia cases in hospital patients receiving heparins, the decrease in their number in intensive care units with the significant decrease in their mortality. The positive results of the introduction of the rule and the algorithm were especially noticeable in cardiac surgery, traumatology, urology and vascular surgery. Severe thrombocytopenia (<100×109/L) in COVID‑19 was detected in 168 patients of intensive care units out of 1878 patients treated in the hospital with COVID‑19, which was 8.9%.

Conclusion. The introduction of the original rule for the diagnosis of HIT “100–5–100” and the algorithm for managing of such patients simplified the diagnosis and led to a decrease in the frequency of complications of HIT, including fatal outcomes. Given the almost sevenfold increase in the frequency of suspected HIT in COVID‑19 compared to non-infectious patients, the using of described principles of diagnosis and treatment of HIT could improve the outcomes of this disease as well.

Keywords:heparin; thrombocytopenia; heparin-induced thrombocytopenia; COVID 19; rule for rapid diagnosis of heparin-induced thrombocytopenia

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

For citation: Semigolovskii N.Yu., Drygin A.N., Levchuk A.L., Semigolovskii S.N., Simutis I.S. Heparin-induced thrombocytopenia and COVID‑19: simplified rule of diagnosis and treatment algorithm. Kardiologiya: novosti, mneniya, obuchenie [Cardiology: News, Opinions, Training]. 2022; 10 (2): 18–27. DOI: https://doi.org/10.33029/2309-1908-2022-10-12-18-27 (in Russian)

REFERENCES
1. Glance L.G., Blumberg N., Eaton M.P., et al. Preoperative thrombocytopenia and postoperative outcomes after noncardiac surgery. Anesthesiology. 2014; 120 (1): 62–75.
2. Battistelli S., Genovese A., Gori T. Heparin-induced thrombocytopenia in surgical patients. Am J Surg. 2010; 199 (1): 43–51.
3. Matthai W.H. Thrombocytopenia in cardiovascular patients. Diagnosis and management. Chest. 2005; 127: 46S–52S 19.
4. Favaloro E.J., Henry B.M., Lippi G. The complicated relationships of heparin-induced thrombocytopenia and platelet factor 4 antibodies with COVID-19. Int J Lab Hematol. 2021; 43 (4): 547–58. Epub 2021 March 11. DOI: https://doi.org/10.1111/ijlh.13582
5. Warketin T.E., Greinaher A. Spontaneous HIT syndrome: knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thromb Res. 2021; 204: 40–51. DOI: https://doi.org/10.1016/j.thromres.2021.05.018. Epub 2021 Jun 9.
6. Greinacher А., Thiele Т., Warkentin Т.Е., еt аl. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021; 384 (22): 2092–101. DOI: https://doi.org/10.1056/NEJMoa2104840. Epub 2021 Apr. 9.
7. Lingamaneni P., Gonakoti S., Moturi K., Vohra I., Zia M. Heparin-induced thrombocytopenia in COVID-19. J Investig Med. 2020; (8): 2324709620944091. DOI: https://doi.org/10.1177/2324709620944091
8. Cattaneo M. Thrombosis with thrombocytopenia syndrome associated with viral vector COVID-19 vaccines. Clinical Insights. 2021; 89: 22–24. DOI: https://doi.org/10.1016/j.ejim.2021.05.031
9. Bokeria L.A., Chicherin I.N. Heparin-induced thrombocytopenia (current state of the problem). Мoscow: «NTsSSKh im. A.N. Bakuleva» MZ RF, 2007. 96 p. (in Russian)
10. Warkentin T.E. New approaches to the diagnosis of heparin-induced thrombocytopenia. Chest. 2005; 127: 35–45.
11. Warkentin T.E., Kelton J.G. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001; 344: 1286–92.
12. Eniseeva E.S., Vlasyuk T.P. Acute stent-thrombosis in patient with heparin-induced thrombocytopenia. Sibirskij med. zhurnal [Siberian medical journal]. 2013; (5): 130–1. (in Russian)
13. La Muraglia G.M., Houbballah R., Laposata M. The identification and management of heparin-induced thrombocytopenia in the vascular patient. J Vasc Surg. 2012; 55 (2): 562–70.
14. Poletaeva G.S., Rogal’skaya E.A., Klimovich L.G. et al. Assessment of the incidence of GIT in patients with thrombocytopenia. Materialy XXI Vserossiyskogo sezda serdechno-sosudistykh khirurgov, «NTsSSKh im. A.N. Bakuleva» MZ RF [Materials of the XXI All-Russian Congress of Cardiovascular Surgeons, “A.N. Bakulev NCSSH” of the Ministry of Health of the Russian Federation]. 2015. URL: http://racvs.ru/events/archive/xxi. (in Russian)
15. Battistelli S., Genovese A., Gori T. Heparin-induced thrombocytopenia in surgical patients. Am J Surg. 2010; 199 (1): 43–51.
16. Warkentin T.E., Kelton J.G. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001; 344: 128–692.
17. Warkentin T.E., Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg. 2003; 76: 2121–31.
18. Arepally G.M., Ortel T.L. Heparin-induced thrombocytopenia. Annu Rev Med. 2010; 61: 77–90.
19. Bito S., Miyata S., Migita K., Nakamura M., et al. Mechanical prophylaxis is a heparin-independent risk for anti-platelet factor 4/heparin antibody formation after orthopedic surgery. Blood. 2015 Dec 9. PII: blood-2015-06-651620.
20. Salter B.S., Weiner M.W., Trinh M.A., et al. Heparin-induced thrombocytopenia: a comprehensive clinical review. J Am Coll Cardiol. 2016; 67: 2519–32.
21. Greinacher A. Clinical practice. Heparin-induced thrombocytopenia. N Engl J. 2015; 373: 252–61.
22. Lillo-Le Louët A., Boutouyrie P., Alhenc-Gelas M., et al. Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost. 2004; 2: 1882–8.
23. Cuker A., Arepally G., Crowther M.A., et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost. 2010; 8: 2642–50.
24. Lo G.K., Juhl D., Warkentin T.E., et al. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006; 4 (4): 759–65.
25. Crowther M.A., Cook D.J., Albert M., Williamson D., et al. The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients. J Crit Care. 2010; 25 (2): 287–93.
26. Din F., Kovacs M.J., Butler R., Lazo-Langner A. Inter-observer variability in the assessment of the 4Ts score for the diagnosis of heparin-induced thrombocytopenia in patients undergoing cardiac surgery. Blood. 2009; 114. Abstract 4467.
27. Joseph L., Gomes M.P., Al Solaiman F., et al. External validation of the HIT Expert Probability (HEP) score. Thromb Haemost. 2015; 113 (3): 633–40.
28. Harada M.Y., Hoang D.M., Zaw A.A., et al. Overtreatment of heparin-induced thrombocytopenia in the surgical ICU. Crit Care Med. 2016: 321–40.
29. Berry C., Tcherniantchouk O., Ley E.J., et al. Overdiagnosis of heparin-induced thrombocytopenia in surgical ICU patients. J Am Coll Surg. 2011; 213 (1): 10–17; discussion: 17–18.
30. Semigolovski N. Yu., Semigolovski S.N. Heparin-induced thrombocytopenia in multidisciplinary hospital: the original diagnostic “Rule” and new treatment algorithm is able to reduce mortality rate (a 3-year observation study). The book of abstracts of The Congress on Open Issues in Thrombosis and Hemostasis. Jointly with the 9th Russian Conference on Clinical Hemostasiology and Hemorheology. 2018: 239–40. URL: https://www.isth.org/m/event_details.asp?id=1026831 (in Russian)
31. Gettings M.E., Brush K.A., Van Cott E.M., Hurford W.E. Outcome of postoperative critically ill patients with heparin-induced thrombocytopenia: an observational retrospective case-control study. Critical Care. 2006; 10: R 161. URL: https://doi.org/10.1186/cc5100
32. Pearson M., Nadeau Ch., Blais N. Correlation of ELISA optical density with clinical diagnosis of heparin-induced thrombocytopenia. A retrospective study of 104 patients with positive Anti-PF4/Heparin ELISA. Clin Appl Thromb Hemost. 2014; 20 (4): 349–54.
33. Jang I.K., Hursting M.J. When heparins promote thrombosis: review of heparin-induced thrombocytopenia. Circulation. 2005; 111 (20): 2671–83.
34. Selleng K., Warkentin T.E., Greinacher A: Heparin-induced thrombocytopenia in intensive care patients. Crit Care Med. 2007; 35: 1165–76.
35. Greinacher A., Selleng K. Thrombocytopenia in the Intensive Care Unit Patient. ASH Education Book. 2010; 2010 (1): 135–43.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
CHIEF EDITOR
Andrey G. Obrezan
MD, Professor, Head of the Hospital Therapy Department of the Saint Petersburg State University, Chief Physician of SOGAZ MEDICINE Clinical Group, St. Petersburg, Russian Federation
Journals of «GEOTAR-Media»