Intensive Core ed httpsdotorg/0.1007/00134.024.07478:5 Ten tips on sepsis-induced thrombocytopenia lathan D. Nielsen”? and Lene Russel Marc Leone" ry pet Spine Nate commonly observed phenome- non in sepsis anda frequent cause of anxiety for the clini- cian at the bedside, raising a host of questions, including the concerns about a low platelet count, the interaction between sepsis and platelets, the other causes of throm- bocytopenia, or the indications of platelet transfusion. ‘Though much of the effect of sepsis on platelet physiol- ‘ogy and function is yet unknown, in this article we have undertaken to address many of these common questions. How do we measure platelets? A platelet count is the number of platelets per volume, typically analysed by automated instruments. In cases of abnormal counts, counts are repeated manually. Reported platelet counts are strictly quantitative and qualitative platelet dysfunction can occur in patients with low, normal or elevated platelet counts (1). Platelet function can be affected by drugs, intrinsic platelet dys- function, or renal or liver disease, and unfriendly envi ronments. Specialised assays to measure platelet function exist and viscoelastic testing can provide some qualitative insights but thei clinical relevance is controversial. associated with outcomes ‘Thrombocytopenia (a platelet count 150,000/4L) is common in intensive care unit (ICU) patients [2] and seen in> 55% of sepsis cases and at higher rates in septic shock [3,4]. Severe thrombocytopenia (<50,000/4L) [2] *Corespondence mayckore@ap hm Department of Araethescogy an neni Cae Unt, Noth Hosp Ful outhor svrmation is avaiable ate en of a Springer develops in~30% of thrombocytopenic septic patients 6). ‘Thrombocytopenia in sepsis is associated with worse ‘outcomes [3] and, if early (<24 h) oF sustained, has prognostic utility (3, 4, 6]. However, it remains unclear ‘whether thrombocytopenia in sepsis is an indicator (an affected “innocent bystander") or cause (an “active par- ticipant” in organ injury) of sepsis severity (7]. The risk of ‘coagulation-related complications inereases at< 100,000/ UL, and fear of bleeding complications may prevent clini- ‘ians from performing needed procedures or surgery. Immune mechanisms connect sepsis. to thrombocytopenia Platelets are key players in haemostasis but also have cru- cial roles in inflammation, Immune-mediated platelet activation is an integral infection response, as platelets interact with immune and complement systems, releas- ing agents that promote neutrophil activation and leuko- cyte recruitment, express pattern recognition receptors, ‘and stimulate neutrophil extracellular trap formation (8) Severe thrombocytopenia is associated with dysregu: lated host immunity in septic patients with altered gene ‘expression, including reduced leukocyte adhesion and increased complement signalling (7) Vascular integrity—a link between thrombocytopenia and organ injury Platelets safeguard vascular integrity by optimising the barrier function of microvessels and reducing extrava- sation of both water and plasma proteins, especially in inflammatory states. Platelets directly block gaps in the vascular lining, thereby maintaining endothelial struc tuze, and release soluble factors that enhance endothe- lial barrier function. The loss of endothelium-supporting functions contributes to organ oedema and tissue haem- ‘orthage in sepsis-induced thrombocytopenia (9Sepsis-induced thrombocytopenia is a multifactorial phenomenon, as platelets are irreversibly expended in the immune response. Other aetiologies include entities such as disseminated intravascular coagulation (DIC) and sepsis-associated reactive hemophagocytosis [6]. However, while sepsis isa more common cause of throm- bocytopenia, potentially lethal prothrombotic conditions should always be ruled out. These conditions include heparin-induced thrombocytopenia (HIT), immune- mediated thrombotic thrombocytopenic purpura (IT TP) ‘and haemolytic uremic syndrome (HUS) (Fig. 1). Addi- tional causes include drug-induced pe- nia, immune thrombocytopenia (ITP), haemodilution, pseudo-thrombocytopenia (an in vitro phenomenon ‘caused by ethylenediamine tetraacetic acid (EDTA) that ‘ean be resolved by the use of citrated sample tubes), ‘extracorporeal devices, and_ underlying disease, malignancy or myeloproliferative disorders [10]. ‘A review of the peripheral blood film (“smear”) can be useful in establishing the aetiology of thrombocytopenia, as can bone marrow aspiration in selected circumstances. Antimicrobials can cause thrombocytopenia Drug-induced thrombocytopenia, including that caused by antimicrobials (e.g vancomycin, antifungals, lin- cezolid, beta-lactams, ciprofloxacin [11}) is responsible {for 10-20% of ICU thrombocytopenia cases, and should bbe considered in severe thrombocytopenia (< 20,000/uL) ‘complicated by bleeding, occurring 5-10 days after drug ‘exposure, Stopping the drug if feasible) is recommended, kay, oF n doubt, Seok export advice [Fig.1 How tomanage thrombocytopenia in my patient wth spss IG dseminate Irravescubr coagulation: heparin induced tomb: 20,000/qL. prior to CVC placement and other low-risk procedures, and ‘counts> 50,000/4L prior to lumbar puncture and higher- risk procedures. Take-home message Thrombocytopenia in sepsis is common, but many ies remain. Associations between thrombocy- topenia and bleeding, transfusion, and mortality follow a “dose-response” pattern with worse outcomes accompa- rnying more severe thrombocytopenia, but causality is not established. ‘Advances are required to better understand, and provide optimal support for, septic patients with thrombocytopenia, ‘Author details ssatance Pique Hepa Sewrce es rDes Bure, Universes de Masi ase ies, Medecine Department cI Medicine, Urve'sy of New Meni School cine Abuauerque NM USA Section ef Taruson Mesene bed TheapePattotagy, Department of Fatale, Un Moco Shoo ef Medina Abuqserqu, NM USA Daren of tee Copenhagen erst Hostal Geto senup Denmark. * Depa tment of Cine Med, Unive of Copenhagen Copenhagen, Derm Declarations confit of interest, ML served as peae'fr Shiono and constant for OP Pama a Vas NON serves on soy boadsfrInovem and Adrenomed [sno co fetter acre Publisher's Note Serger ature roma neuraloeth ogo jutiscinal aims in pub ondrtituonal tions Received: 14 February 2024 Accepted: 3 May 2024 Pablished online: 13 May 2024 References Th Hucban Hater LA (198) Okordes of latte function - mechan, ‘dagnots and management West J ed 134108-127tpa/09.009/10. Jonson Af yg SL, Hideband Tt 2021 Tembecyroperia in ixense cae unt paientsascoprgreew. Ai Anaesiesl Scand (652-14 tpe/o.0r/10111Vsa613650| 3. Anthan 7, Pine Peer Atl 2023) trastusontiniCU patlens an erst Intensive Cre Med 491327 bcytpenia aed pate 3 nceion conor sty 338 htps//do.g 01007eu, Fougue , Carpenter Jet al 2028) Cnc inion of tom ‘oytapeniain tins with sept shock an cbsenatioa respecte stay Jn Cae 765493 Mip/ fer 0016 700318093 oyoma ator Muren etal UB) Tine couse of mature ‘pte count ri elon 6 svorboryecrna and mest n ents vith sep PLaSONE 131-16 npn/en.og/10137 uns, poneoisatet “hole F Sere Sain A Rigi eta 2013) Feidemctog and out come ofthorrocyopenic pins nthe sense cate unt rests 2 ‘rospecive multicenter sud tensive Care Ned 31460 168 P/ Sotor/10 007 sc0134 01325693 CCousisTAM Van Yught LA Scicura Be 201 Themboey topenia is asscated witha dystequsted host response ncticaly [sep patere Bld 17202-9072 tp /30.09/10 11807 ‘lone 2015 1-680744 (CSR Ma AC Taever SA etal 0007 atl TA actnates pete phlewtacl tps terre actor sep Dd Nat Med 1303-468 mgs Hoko'/10038/0n 1565 Hot No Demers iA Wogne 05 G01?) How poets safeguard ‘salar neg) Thom laemst 956-65 htge/o.079/101 115. S38 763620"1 00217 ba. Lew Mada H tal 0015 Ofer proses for sepss- Induced diserinates vas coogi: commuancton rm the SS fhe SM. Thom Haemort 1715-419. nips//Soixg 0 Tit 354 Scher 2012) Orgs that afc pateletancion Sane Them eros 38:855-883.ips//dlor/055/-032-132888) Mari, Ua Gana, Bichou T2022) Team of rp nduced Immune hromeytopenias. Haematioyca 107 1261-1277 maps//6 frg/10332¢haemtaL 2021279484 Fussell, Host 8 Kelen et a 2017 ks of hein and tomibo- SSshntersvecare unt paterts wth harmatlegea ragrancies Ae Intense Cte 7.18. Naps //Slor/I00 16/5361 0174340 Csi anger Seales OC al 204) venous hromboematsm ‘nerd pavents wih erate masgrarcy- a popelson- ‘ese coor study arse Cae Med 50222 238 hps/is0r/0 Tgrsen94-003.070872 iu 5.Chen Pans zhoy A 2022 Poteet wanton and meray In pens wih sepsisinduces evomboeytapens: a prepensty core ‘matching anal Nou Sang 117187-T18 p/.cg/10 17a Ts anor van de West von er Ven WM et 2025) Pet {Wasson bore eve placement pats wth twombocytonenN gl Me 388 1956-1055 ps/o.09/101S6MEMoa2794322