Coagulation panel tests could be life saving in severe infections

Coagulation panel tests could be life saving in severe infections

Editors:

  1. Dr. Praful B. Godkar (Ph.D)
    Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD.
  2. Dr. Gauri Kulkarni MD (Pathology)
    Vice President, AGD Biomedicals (Pvt) LTD.

Patients suffering from severe infections (viral, bacterial or parasitic) may lead to sepsis leading to hemostatic abnormalities, such as disseminated intravascular coagulation (DIC) with thrombocytopenia(1-4). Coagulation abnormalities may significantly contribute to morbidity and mortality.   Deranged coagulation disorders require specific therapeutic and supportive management. Prompt analysis of coagulation disorders using coagulation tests is useful to establish the underlying cause and to initiate corrective and supportive treatment(4-7). The clinical management of coagulation disorders in critically ill patients can be facilitated through blood testing using coagulation analyzers such as the AGD C-102(9). This approach will assist clinicians in formulating optimal diagnostic and therapeutic strategies in treating coagulation abnormalities related to sepsis.

NOTE:

Sepsis is a significant cause of maternal, neonatal and child mortality. It is necessary  to achieve universal prevention, diagnosis and management of sepsis(7).

Q1. What is hemostasis?

ANS: Hemostasis is a complex process which causes the bleeding process to stop. It refers to the process of keeping blood within a damaged blood vessel.

Q2. What are blood coagulation factors?

ANS Blood coagulation factors are about 13 proteins in blood circulation. These are in the inactivated form. However, following internal or external injury, these coagulation factors become activated in a controlled manner and with the help of accumulated platelets form blood clots to stop bleeding. Therefore, blood coagulation factors are essential components in the process of hemostasis.

NOTE :

Blood coagulation factors are: Factor I (Fibrinogen), Factor II (Prothrombin), Factor III (Tissue thromboplastin), Factor IV (calcium ions), Factor V(Labile factor: Proaccelerin), Factor VI (Va: accelerin + V), Factor VII (Proconvertin), Factor VIII (Antihemophilic factor ’A’, Factor IX (antihemophilic factor B (Christmas factor), X (Stuart factor), Factor XI (Plasma thromboplastin antecedent), Factor XII (Hageman (or contact) factor, Factor XIII (Fibrin stabilizing factor). 

Additional supportive proteins: Prekallikrein and High molecular weight kininogen (HMWK) along with Protein C and Protein S.

Q3. What are important Coagulation panel tests?

ANS (9):

(A) Prothrombin time (PT)

(B) Activated Partial thromboplastin time (aPTT)

(C) Thrombin time (TT)

(D) Fibrinogen determination

(E) Platelet count.

Q4. What is the significance of Coagulation panel tests?

ANS

Coagulation panel tests are very important for the following reasons:

 (A) To determine blood clotting ability in severe infections

 (B) To diagnose bleeding disorders,

 (C) To monitor anticoagulant therapy (such as heparin and warfarin)

 (D) To evaluate bleeding risk before surgery.

 (E) To evaluate thrombocytopenia (decrease in platelet count).

NOTE (9):

(A) Prolonged PT and aPTT: Indicate a defect in the common clotting pathway, which involves factors I, II, V,  X and XII.

(B) Normal PT, and prolonged  aPTT: Indicate a defect in the intrinsic pathway,  involving factor VIII, IX,  X, XI, XII.

(C ) Abnormal PT, Normal aPTT: Indicate a defect in the extrinsic pathway, potentially a deficiency in factors II, V, VII and X.

(D) Hemophilia A and B (congenital disorders) can be diagnosed using aPTT test, which indicate prolonged blood clotting time.

(E ) Clotting factor VIII deficiency leads to Hemophilia A and clotting factor IV deficiency leads to Hemophilia B.

(F) The main treatment on Hemophilia A and Hemophilia B is replacement of respective missing clotting factors.

CASE STUDY

A 58-year-male was presented with fever, chills, severe headache, myalgia and deep bone pain. Blood smears were prepared (during fever) and stained using Field stain. Observations of stained smears under microscope did not show presence of malarial parasites on two consecutive days. His platelet count was 55,000/cmm (Normal range: 2,50,000–5,00,000/cmm).

The following were additional tests performed on his blood sample:

Dengue NS1 Ag assay: Positive

COAGULATION PANEL TESTS

PARAMETERRESULTNORMAL RANGE
Prothrombin time (PT)19 seconds12 – 16 seconds
Activated partial thromboplastin time: (APTT)44 seconds35 – 40 seconds
Thrombin time (TT)24 seconds15 – 20 seconds

EVALUATION OF LABORATORY REPORTS

(A) Patient was suffering from Dengue fever, and related thrombocytopenia, prolonged   PT,  APTT and TT.

(B) Prolonged PT, aPTT and TT signify a defect in the common pathway of the coagulation cascade.

(C) A high TT, along with high PT and aPTT, provides strong evidence of a defect with the final stages of coagulation that increases the risk of bleeding(9).

Note (3-6, 10)

(A) Severe dengue virus infection may lead to sepsis.

(B) Nonstructural protein NS1 of Dengue virus binds to prothrombin and inhibits prothrombin activation.

(C) Both severe dengue and sepsis involve endothelial dysfunction and increased vascular permeability, which can lead to plasma leakage and shock.

(D) Dengue infection affects coagulation factors, primarily by leading to prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), decreased fibrinogen levels, and increased D-dimer levels. This is caused by the viral infection of liver, which leads to decrease in the production of coagulation factors.

(E) Screening and early correction of coagulation abnormalities could be helpful to reduce related complications. Incidences of deaths of patients due to shock in severe dengue infections have been documented(3,4,7).

(F) It is common for a dengue infection to become complicated by a secondary bacterial infection, leading to concurrent sepsis(5).

References

(1) Fleischmann-Struzek C, Rudd K. Challenges of assessing the burden of sepsis. Med Klin Intensivmed Notfmed. 2023 Dec;118(Suppl 2):68-74. doi: 10.1007/s00063-023-01088-7.

(2) Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.

(3) Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504–7. pmid:23563266

(4) Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30(4):536–55. Epub 2004/03/05. pmid:14997291

(5) Premaratna R, Dissanayake D, Silva FH, et al. Secondary bacteremia in adult patients with prolonged dengue fever. Ceylon Med J 2015; 60: 10–12.

(6) 1. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, Wilmer A, Bobbaers H: Thrombocytopenia and prognosis in intensive care. Crit Care Med 2000, 28:1871-1876.

(7) MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M: Early coagulopathy predicts mortality in trauma. J Trauma 2003, 55: 39-44.

(8) Oppenheim-Eden A, Glantz L, Eidelman LA, Sprung CL: Spontaneous intracerebral hemorrhage in critically ill patients: incidence over six years and associated factors. Intensive Care. Med 1999, 25:63-67.

(9) Godkar PB, Godkar DP. Text book of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.

(10) Singhi S, Kissoon N, Bansal A. Dengue and dengue hemorrhagic fever: management issues in an intensive care unit. Jornal de pediatria. 2007; 83(2):S22–S35.

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