Heparin-induced Thrombocytopenia: Pathophysiology, Diagnosis and Management

Patriarcheas, Vasileios; Pikoulas, Antonios; Kostis, Minas; Charpidou, Andriani; Dimakakos, Evangelos

doi:10.7759/cureus.7385

Cited by 24 publications

(20 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heparin-induced Thrombocytopenia (HIT) is an immune system response in which the platelet factor 4 (PF4) forms an immune complex with heparin and immunoglobulin G (IgG). The formed immune complex binds to the platelet surface receptors which results in platelet destructions and thrombocytopenia [31,32]. Besides, heparin could result in elevated INR levels [33] as it was observed in thrombocytopenic patients (case group).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors of Hospital-acquired Thrombocytopenia in Toxicological Intensive Care Unit

Talaie

Hosseini

Nazari

et al. 2020

IJMTFM

View full text Add to dashboard Cite

Background: Platelet count is a readily available biomarker predicting disease severity and risk of mortality in the intensive care units (ICU). This study aims to describe the frequency, to assess the risk factors, and to evaluate the impact of thrombocytopenia on patient outcomes in a Toxicological ICU (TICU).Methods: In this prospective observational Cohort study, we enrolled 184 patients admitted to our TICU from October 1st, 2019, to August 23rd, 2020. Mild/moderate and severe thrombocytopenia were defined as at least one platelet counts less than 150×103/μL and 50×103/μL during the ICU stay, respectively.Results: Of 184 enrolled patients, 45.7% had mild to moderate thrombocytopenia and 5.4% had severe thrombocytopenia. Old age (OR: 1.042, 95%CI: 1.01-1.075, P=0.01), male gender (OR: 4.348, 95%CI: 1.33-14.22, P=0.015), increased international normalized ratio (INR) levels (OR: 3.72, 95%CI: 1.15-112, P=0.028), and administration of some medications including heparin (OR: 3.553, 95%CI: 1.11-11.36, P=0.033), antihypertensive drugs (OR: 2.841, 95%CI: 1.081-7.471, P=0.034), linezolid (OR: 13.46, 95%CI: 4.75-38.13, P<0.001), erythromycin (OR: 19.58, 95%CI: 3.23-118.86, P=0.001), and colistin (OR: 10.29, 95% CI 1.44-73.69, P=0.02) were the risk factors of hospital-acquired thrombocytopenia. The outcomes of patients with normal platelet count were significantly better than those who developed thrombocytopenia (P<0.001).Conclusion: We found that thrombocytopenia could develop in almost 50% of patients admitted to TICU, which is associated with poor prognosis. Additionally, the platelet counts should be closely monitored to administer some medications (heparin, antihypertensive drug, and linezolid), especially in old patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Risk Factors of Hospital-acquired Thrombocytopenia in Toxicological Intensive Care Unit

Talaie

Hosseini

Nazari

et al. 2020

IJMTFM

View full text Add to dashboard Cite

show abstract

“…deterioration of respiratory function, relapse of fever or persistence of fever after five days of hospitalization, increase in D-Dimers or decrease in platelet count compared to admission values) ( Figure 1). Secondary outcomes included: (i) inflammatory biomarkers in patients treated with intermediate dosage vs. those treated with other (or no) anticoagulation regimens; and (ii) safety of anticoagulation treatment measured as incidence of bleeding events, heparininduced thrombocytopenia (HIT) (35) or allergic reactions.…”

Section: Ethra Anticoagulation Protocol For Hospitalized Covid-19 Patmentioning

confidence: 99%

Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study

Poulakou

Dimakakos

Κόλλιας

et al. 2021

In Vivo

Self Cite

View full text Add to dashboard Cite

“…In HIT, the engagement of PF4 by PF4 autoantibodies on heparin-decorated endothelial cells ultimately serves to engage and activate platelet FcRγII receptors, with platelet alpha granule degranulation followed by further PF4 release and progressive immunothrombosis [ 51 ] - including autoantibody-PF4 immune complex activation of myeloid cells [ 52 , 53 ]. Following heparin therapy for thromboembolic disease, heparin sequestration and further PF4 entrapment may cause clot extension and new thromboembolism [ 54 ]. It has been deduced that PF4-polyanionic molecular interactions and PF4 autoantibodies may be a common feature of naturally-occurring immune responses that is recapitulated with pharmacological application of heparin [ 46 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Immunothrombosis in Vaccine-Induced Thrombotic Thrombocytopenia (VITT) Compared to Natural SARS-CoV-2 Infection

McGonagle

Marco

Bridgewood

2021

Journal of Autoimmunity

137

128

View full text Add to dashboard Cite

Herein, we consider venous immunothrombotic mechanisms in SARS-CoV-2 infection and anti-SARS-CoV-2 DNA vaccination. Primary SARS-CoV-2 infection with systemic viral RNA release (RNAaemia) contributes to innate immune coagulation cascade activation, with both pulmonary and systemic immunothrombosis - including venous territory strokes. However, anti-SARS-CoV-2 adenoviral-vectored-DNA vaccines -initially shown for the ChAdOx1 vaccine-may rarely exhibit autoimmunity with autoantibodies to Platelet Factor-4 (PF4) that is termed Vaccine-Induced Thrombotic Thrombocytopenia (VITT), an entity pathophysiologically similar to Heparin-Induced Thrombocytopenia (HIT). The PF4 autoantigen is a polyanion molecule capable of independent interactions with negatively charged bacterial cellular wall, heparin and DNA molecules, thus linking intravascular innate immunity to both bacterial cell walls and pathogen-derived DNA. Crucially, negatively charged extracellular DNA is a powerful adjuvant that can break tolerance to positively charged nuclear histone proteins in many experimental autoimmunity settings, including SLE and scleroderma. Analogous to DNA-histone interactons, positively charged PF4-DNA complexes stimulate strong interferon responses via Toll-Like Receptor (TLR) 9 engagement. A chain of events following intramuscular adenoviral-vectored-DNA vaccine inoculation including microvascular damage; microbleeding and platelet activation with PF4 release, adenovirus cargo dispersement with DNA-PF4 engagement may rarely break immune tolerance, leading to rare PF4-directed autoimmunity. The VITT cavernous sinus cerebral and intestinal venous territory immunothrombosis proclivity may pertain to venous drainage of shared microbiotal-rich areas of the nose and in intestines that initiates local endovascular venous immunity by PF4/microbiotal engagement with PF4 autoantibody driven immunothrombosis reminiscent of HIT. According to the proposed model, any adenovirus-vectored-DNA vaccine could drive autoimmune VITT in susceptible individuals and alternative mechanism based on molecular mimicry, vaccine protein contaminants, adenovirus vector proteins, EDTA buffers or immunity against the viral spike protein are secondary factors. Hence, electrochemical DNA-PF4 interactions and PF4-heparin interactions, but at different locations, represent the common denominator in HIT and VITT related autoimmune-mediated thrombosis.

show abstract

Heparin-induced Thrombocytopenia: Pathophysiology, Diagnosis and Management

Cited by 24 publications

References 48 publications

Risk Factors of Hospital-acquired Thrombocytopenia in Toxicological Intensive Care Unit

Risk Factors of Hospital-acquired Thrombocytopenia in Toxicological Intensive Care Unit

Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study

Mechanisms of Immunothrombosis in Vaccine-Induced Thrombotic Thrombocytopenia (VITT) Compared to Natural SARS-CoV-2 Infection

Contact Info

Product

Resources

About