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SPCI - Sociedade Portuguesa de Cuidados Intensivos

Revista Brasileira de Terapia Intensiva

AMIB - Associação de Medicina Intensiva Brasileira


ISSN: 0103-507X
Online ISSN: 1982-4335

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Crochemore T, Savioli FA, Pessoa CM, Resende AA, Narciso RC. Efeito compensatório do fibrinogênio em paciente com aplasia de medula óssea, choque séptico e trombocitopenia grave guiado por tromboelastometria: relato de caso. Rev Bras Ter Intensiva. 2018;30(3):394-397





Compensatory effect of fibrinogen in a patient with bone marrow aplasia, septic shock, and severe thrombocytopenia guided by thromboelastometry: a case report

Efeito compensatório do fibrinogênio em paciente com aplasia de medula óssea, choque séptico e trombocitopenia grave guiado por tromboelastometria: relato de caso

Tomaz Crochemore1, Felicio Aragão Savioli1, Camila Menezes Pessoa1, Adriana Abreu Resende1, Roberto Camargo Narciso1

1 Intensive Care Unit, Hospital Leforte Morumbi - São Paulo (SP), Brazil.

Conflicts of interest: None.

Responsible editor: Leandro Utino Taniguchi

Submitted on February 16, 2018
Accepted on May 21, 2018

Corresponding author: Tomaz Crochemore, Unidade de Terapia Intensiva, Hospital Leforte Morumbi, Rua Três Irmãos, 190, Zip code: 05615-190 - São Paulo (SP), Brazil, E-mail:



Platelet transfusion is a common practice to prevent spontaneous bleeding or bleeding due to invasive procedures. Transfusion of allogeneic blood components is associated with increased mortality and a worse clinical outcome. The clot strength is assessed by thromboelastometry and determined by the interaction between platelets and fibrinogen. The compensatory effect of high levels of fibrinogen on clot strength in patients with thrombocytopenia has been demonstrated in different clinical settings including sepsis. We report the case of a patient with severe thrombocytopenia whose thromboelastometry showed clot strength that was compensated for by the increase in plasma fibrinogen levels as an acute phase reactant of septic patients. Here, we report a case of a 62-year-old female diagnosed with bone marrow aplasia admitted in the intensive care unit with septic shock and severe thrombocytopenia. During the first 24 hours in the intensive care unit, she presented acute respiratory insufficiency and circulatory shock. The use of invasive mechanical ventilation and norepinephrine was required. Her chest X-ray showed bilateral lung injury. Thus, bronchoscopy with bronchoalveolar lavage was requested. Thromboelastometry was performed and resulted in a normal coagulable profile. Despite severe thrombocytopenia (1,000/mm3), fibrinogen levels were increased (1,050mg/dL) due to septic shock. Bronchoscopy was performed without any active or further bleeding. Here, we report the use of thromboelastometry in the diagnosis of coagulation disorders, preventing unnecessary prophylactic platelet transfusion.

Keywords: Thromboelastography; Thrombocytopenia; Fibrinogen; Septic shock; Bone marrow diseases; Bone marrow/abnormalities.



The cell-based model of coagulation described in 2001 by Hoffman et al., demonstrated the importance of the membrane surface of cells for thrombin generation and clot formation, whose initial trigger is determined by the tissue factor released by the endothelium. The process of clot formation is composed of four consecutive phases: initiation, amplification, propagation and stabilization of the clot. The extrinsic and intrinsic pathway of coagulation function in a dependent and sequential way in the initial phases for the production of thrombin.(1)

Conventional coagulation tests such as activated partial thromboplastin time or prothrombin time are weak predictors of bleeding in critically ill patients.(2) Conventional coagulation tests fail to identify hypercoagulability and hyperfibrinolysis, accessing only 5% of the thrombin generation.(2,3)

Viscoelastic tests allow for early detection of coagulopathy and can predict massive transfusion. Viscoelastic tests can also guide goal-directed therapy with specific hemostatic drugs, coagulation factor concentrates, and allogeneic blood products.(4,5)

Fibrinogen is an acute phase protein that is synthesized in the liver in response to inflammatory signals. The concentration of fibrinogen increases with inflammation including sepsis.(6) Both the fibrinogen levels and the platelet count are determinants of clot strength as shown by the maximum clot firmness (MCF), which is a parameter of rotational thromboelastometry.(7,8)

We report a clinical case of a septic patient marked by severe thrombocytopenia owing to bone marrow aplasia. Bronchoscopy was required due to acute respiratory impairment, and rotational thromboelastometry was performed to guide the transfusion and maintain safety during the procedure. No local or distant bleeding was observed in the patient.


A 62-year-old female, with primary bone marrow aplasia was admitted in the intensive care unit (ICU) with septic shock, hematomas and petechiae spread throughout the body. A physical examination revealed impaired conscious level, tachycardia, and hypotension. Laboratory examination revealed the following: hemoglobin 8.2g/dL, leukocytes 290/mm3, platelets 1000/mm3, fibrinogen 1050mg/dL, international normalized ratio 1.1, C-reactive protein 52mg/dL, and creatinine 1.1mg/dL (Table 1). Orotracheal intubation was performed due to respiratory insufficiency and an impaired conscious level. Norepinephrine and antibiotics were started. A computed tomography was performed showing bilateral alveolar infiltrate. Bronchoscopy and bronchoalveolar lavage were requested to investigate the etiological cause. Due to severe thrombocytopenia, thromboelastometry was requested to determine whether the bronchoscopy could be performed safely. EXTEM (Extrinsic rotational thromboelastometry) showed MCF of 50 millimeters (mm), ML (Maximum Lysis) of 0%, and FIBTEM (Fibrinogen rotational thromboelastomery) showed MCF of 40mm (Figure 1 and Table 2). The patient presented with a normal coagulable profile according to thromboelastometry even with extremely low platelet quantitative levels (1000/mm3). Bronchoscopy was safely performed with signs of bilateral alveolar hemorrhage, with the presence of organized clots in the inferior lobe segment but without active bleeding. The patient was extubated seven days after bronchoscopy, without any signs of bleeding. Laboratory test results showed an increase in platelet counts as well as a reduction in fibrinogen concentration with the improvement of sepsis (Figure 2). She was discharged from the ICU three days after extubation.

Table 1 - Laboratory results
Laboratory tests Results Reference range
Hemoglobin 8.2g/dL 12 - 16g/dL
Leukocytes 290/mm3 4,000 - 11,000/mm3
Platelet count 1,000/mm3 150,000 - 450,000/mm3
Fibrinogen 1,050mg/dL 200 - 400mg/dL
INR 1.1 0.9 - 1.3
CRP 52mg/dL < 3mg/dL
Creatinine 1mg/dL 0.5 - 1.1mg/dL

INR - International Normalized Ratio; CRP - C-reactive protein.

Table 1 - Laboratory results

Figure 1 - Results of thromboelastometry.

Table 2 - Thromboelastometry analysis
CT (s) 80 77
CFT (s) 50 58
A 5 (mm) 33 29
A 10 (mm) 40 33
MCF (mm) 50 40
ML (%) 0 0

ROTEM - Rotational thromboelastometry; EXTEM - extrinsic rotational thromboelastometry; FIBTEM - Fibrinogen rotational thromboelastometry - clot firmness; CFT - clot formation time; A5 - amplitude 5; A10 - amplitude 10; MCF - maximum clot firmness; ML - maximum lysis.

Table 2 - Thromboelastometry analysis

Figure 2 - Evolution of platelet count and fibrinogen concentration.


We aim to discuss the routine practice of platelet transfusion. This case report is an example of how prophylactic transfusion can be avoided using viscoelastic tests. We discuss a patient with severe thrombocytopenia associated with bone marrow aplasia who presented with septic shock and acute respiratory failure requiring mechanical ventilation. Bronchoscopy and bronchoalveolar lavage were requested for diagnosis. Thromboelastometry was performed to guide transfusion, and therapy was normal. This case illustrates the compensatory effect of increased fibrinogen as an acute phase reactant during sepsis on blood coagulability, even in patients with severe thrombocytopenia.

Thromboelastometry is a useful test for diagnosing blood disorders and for managing bleeding in critical care patients. In several cohort studies, bleeding management guided by thromboelastometry has been associated with a reduction in transfusion requirements and also a reduction in the incidence of transfusion-related adverse events, with a better patient outcome.(9-11)

Thrombocytopenia is not ideal for patients with bone marrow aplasia, which increases their exposure to blood products. As shown, the isolated platelet count is a poor predictor for bleeding risk. Nevertheless, the prophylactic use of platelet concentrates is quite common in many centers to prevent bleeding in patients undergoing invasive procedures or surgery.(12)

Massion et al. proposed that the increased fibrinogen concentration in septic patients may explain the discrepancy between low platelet levels and normal maximum clot firmness in thromboelastometry by compensating for thrombocytopenia or for decreased coagulation factor activity.(13,14)

Fibrinogen (factor I) is a soluble glycoprotein synthesized in the liver that plays a central role in the clot formation and stabilization process. It acts as the precursor of fibrin that gives a substrate to blood clots and also promotes platelet aggregation and fibrinolysis. The increased levels of fibrinogen in the blood lead to enhancement in platelet interaction due to increased binding to the platelet glycoprotein IIb/IIIa receptor and fibrinolysis impairment. Fibrinogen is an acute phase plasma protein whose synthesis and circulating concentration are upregulated in response to inflammation, infection and tissue injury, such that its blood concentration may increase up to ten-fold, enhancing thrombus formation by altering the kinetics of coagulation.

Clot strength as assessed by the MCF, a parameter of rotational thromboelastometry, is highly influenced by both fibrinogen levels and platelet count.(7,8) The minimal platelet count for normal clot formation on viscoelastic tests is strongly affected by the fibrinogen level. Other than the platelet count, the MCF was the most important parameter in predicting bleeding in patients with idiopathic thrombocytopenic purpura.(15)

Therefore, patients with severe thrombocytopenia as we report in this case could benefit from thromboelastometry assessment in order to predict bleeding and avoid unnecessary transfusion, since platelets alone are not a good predictor of bleeding.


Thromboelastometry used as a diagnostic tool for a clotting disorder prevented unnecessary prophylactic platelet transfusion considering the compensatory effect of increased fibrinogen concentration by sepsis, even in a patient with extremely severe thrombocytopenia. We believe that thromboelastometry may be a safer and more effective option in predicting the bleeding risk than isolated platelet counts in critically ill patients.


We would like to thank the multidisciplinary intensive care unit team at Hospital Leforte for their support.


Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001;85(6):958-65. Link DOILink PubMed
Lier H, Böttiger BW, Hinkelbein J, Krep H, Bernhard M. Coagulation management in multiple trauma: a systematic review. Intensive Care Med. 2011;37(4):572-82. Link DOILink PubMed
Crochemore T, de Toledo Piza FM, Silva E, Corrêa TD. Thromboelastometry-guided hemostatic therapy: an efficacious approach to manage bleeding risk in acute fatty liver of pregnancy: a case report. J Med Case Rep. 2015;9(1):202. Link DOI
Crochemore T, Piza FM, Rodrigues RD, Guerra JC, Ferraz LJ, Corrêa TD. A new era of thromboelastometry. Einstein (Sao Paulo). 2017;15(3):380-5. Link DOILink PubMed
Pezold M, Moore EE, Wohlauer M, Sauaia A, Gonzalez E, Banerjee A, et al. Viscoelastic clot strength predicts coagulation-related mortality within 15 minutes. Surgery. 2012;151(1):48-54. Link DOILink PubMed
Jain S, Gautam V, Naseem S. Acute-phase proteins: As diagnostic tool. J Pharm Bioallied Sci. 2011;3(1):118-27. Link DOILink PubMed
White NJ, Newton JC, Martin EJ, Mohammed BM, Contaifer D Jr, Bostic JL, et al. Clot Formation is associated with fibrinogen and platelet forces in a cohort of severely injured emergency department trauma patients. Shock. 2015;44 Suppl 1:39-44. Link DOILink PubMed
Lang T, Toller W, Gütl M, Mahla E, Metzler H, Rehak P, et al. Different effects of abciximab and cytochalasin D on clot strength in thrombelastography. J Thromb Haemost. 2004;2(1):147-53. Link DOILink PubMed
Schöchl H, Nienaber U, Maegele M, Hochleitner G, Primavesi F, Steitz B, et al. Transfusion in trauma: thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Crit Care. 2011;15(2):R83. Link DOILink PubMed
Nienaber U, Innerhofer P, Westermann I, Schöchl H, Attal R, Breitkopf R, et al. The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. Injury. 2011;42(7):697-701. Link DOILink PubMed
Johansson PI, Stensballe J, Ostrowski SR. Current management of massive hemorrhage in trauma. Scand J Trauma Resusc Emerg Med. 2012;20:47. Link DOILink PubMed
Greene LA, Chen S, Seery C, Imahiyerobo AM, Bussel JB. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol. 2014;166(4):592-600. Link DOILink PubMed
Massion PB, Peters P, Ledoux D, Zimermann V, Canivet JL, Massion PP, et al. Persistent hypocoagulability in patients with septic shock predicts greater hospital mortality: impact of impaired thrombin generation. Intensive Care Med. 2012;38(8):1326-35. Link DOILink PubMed
Scarlatescu E, Lancé MD, White NJ, Arama SS, Tomescu DR. Effects of malignancy on blood coagulation in septic intensive care patients. Blood Coagul Fibrinolysis. 2018;29(1):92-6. Link DOILink PubMed
Gunduz E, Akay OM, Bal C, Gulbas Z. Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura? Platelets. 2011;22(7):516-20. Link DOILink PubMed

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