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N. Amin and V. Patil



Step 8: Use less allergenic blood products

In patients with multiple blood transfusion and transfusion-related complications, alternatively processed blood products should be considered (Table 61.1).

Step 9: Consider threshold for blood transfusion

If the bleeding has stopped and serum lactate is normal, do not transfuse any more blood or blood products.

In the absence of active bleeding, keep a transfusion threshold of less than 7.0 g% and keep 7–9 g/dL Hb in critically ill patients who are hemodynamically stable.

RBC transfusion may be beneficial in anemic patients with acute coronary syndrome (keep Hb >10 g/dL).

Step 10: Use blood products judiciously

In the absence of bleeding, do not correct high INR with FFP.

Patients having inadequate intake or on anticoagulants and broad-spectrum antibiotics are likely to have vitamin K deficiency, which can cause deranged INR.

They will benefit from intravenous vitamin K supplementation.

Suggested Reading

1.Napolitano LM, Kurek S, American College of Critical Care Medicine of the Society of Critical Care Medicine, Eastern Association for the Surgery of Trauma Practice Management Workgroup. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med. 2009;37:3124–57.

These are evidence-based guidelines on the use of RBC transfusions in adult trauma and critical care endorsed by SCCM.

2.Klein HG, Spahn DR. Series on transfusion medicine. Lancet. 2007;370:415–48.

An excellent review on red cell transfusion, platelet transfusion, and coagulation factor concentrates.

3.BCSH. Guidelines for management of massive blood loss. Br J Haematol. 2006;135:634–41.

It is an evidence-based guideline on management of massive blood loss.





Disseminated Intravascular Coagulation


and Thrombocytopenia

Vijaya Patil, Nayana Amin, Reshma Ambulkar,

and Atul Kulkarni

A 40-year-old male patient was admitted with acute pancreatitis. He developed fever, tachycardia, hypotension, and respiratory distress on the third day of admission. His abdomen was severely tender and distended. Next morning the nurse noticed excessive oozing from arterial and central line insertion site, and his abdomen was further distended.

Bleeding manifestation due to disseminated intravascular coagulation (DIC) occurs in 1% of hospital admission. Assessing and managing these patients require a systematic approach as DIC is a reflection of underlying systemic disease affecting the coagulation system, resulting in procoagulant activation, fibrinolytic activation, consumption coagulopathy, and end organ damage, which needs to be recognized and treated.

Step 1: Initial resuscitation

Special emphasis should be placed on stabilizing hemodynamics, and if needed, blood and blood product transfusion should be started.

Care should be taken in establishing venous access in actively bleeding patients who may be coagulopathic.

Peripheral access is preferable to central.

Use ultrasound-guided venous cannulation if possible and preferably choose compressible sites like internal jugular or femoral vein.

Avoid arterial punctures.

V. Patil, M.D. (*) • N. Amin, M.D. • R. Ambulkar, M.D., F.R.C.A. • A. Kulkarni, M.D. Department of Anaesthesia, Critical Care & Pain, Tata Memorial Hospital,

Mumbai, India

e-mail: vijayappatil@yahoo.com

R. Chawla and S. Todi (eds.), ICU Protocols: A stepwise approach,


DOI 10.1007/978-81-322-0535-7_62, © Springer India 2012



V. Patil et al.


Table 62.1 Conditions associated with DIC


Bacterial—Gram-negative and Gram-positive sepsis


Viral—cytomegalovirus, HIV, hepatitis, dengue




Parasitic—malaria, leptospirosis


Solid tumors


Hematological—acute promyelocytic leukemia is


commonly associated with DIC


Amniotic fluid embolism


Placenta abruption




Intrauterine fetal death/retained products of conception

Toxic and immunological insults

Viper snake bites


Massive transfusion


ABO transfusion incompatibility


Transplant rejection

Massive inflammation

Severe trauma


Crush injuries


Massive burns


Fulminant liver failure


Severe hypo-/hyperthermia


Severe pancreatitis

Vascular disorders

Aortic aneurysms


Giant hemangiomas

Step 2: Take relevant history and perform focused physical examination

Take history of known systemic conditions associated with DIC and coagulation disorders (Table 62.1).

Review the drug history, particularly the use of heparin and warfarin, and consumption of antiplatelet agents including nonsteroidal anti-inflammatory drugs.

Look for bleeding manifestation, superficial like skin and mucosal (petechiae, purpura) or visceral and deep seated (gastrointestinal bleeding).

Look for thrombotic manifestations like deep vein thrombosis (DVT) of lower limbs or venous or arterial thrombosis at any other site (e.g., cerebral).

Step 3: Investigate to ascertain the type and cause of bleeding (Table 62.2)

Complete blood count, including platelet count and peripheral smear, for the presence of fragmented RBCs.

Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT).

Fibrinogen level, fibrin degradation product (FDP), D-dimer.

Renal and liver function tests.

The commonest laboratory abnormality is thrombocytopenia followed by elevated FDPs, prolonged PT, prolonged APTT, and a low fibrinogen.

Table 62.2 Coagulation profile




What does it monitor

Normal value


Prothrombin time

Factors that are in the extrinsic

11–13 s

Prolongation of the PT is most often a result of deficiencies in factor


pathway and common pathway:


VII but can also be caused by any of the extrinsic and common


factors VII, X, V, and II


pathway factors. Decreased fibrinogen, levels less than 100 mg/dL,




will also prolong the PT




Cholestatic jaundice




Acute or chronic liver failure












Vitamin K deficiency




Coumadin (warfarin) therapy




Factors I, II,V, VII, X deficiency

Activated partial

Factors that are designated in the

28–34 s

Heparin therapy

thromboplastin time

intrinsic pathway: factors XII, XI,


Factor deficiency


IX, VIII, X, V, II, and fibrinogen


Presence of an inhibitor like lupus anticoagulants




Platelet count

Quantifies platelet number

130–400 × 109/L

Decreased production (bone marrow disorder), increased destruction,




idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocy-




topenic purpura, sequestration (hypersplenism)

Thrombin time

Evaluates the last step of

13–15 s

Heparin therapy


coagulation (conversion of




fibrinogen to fibrin)


Qualitative fibrinogen abnormalities or hypofibrinogenemia







Elevated FDPs (fibrin degradation products)

Fibrinogen level


200–500 mg/dL

Congenital and acquired hypofibrinogenemia






Cross-linked D fragments of the

500 ng/mL

Deep venous thrombosis, DIC, pulmonary embolism, thrombolytic


protein fibrinogen


treatment, postoperative

Thrombocytopenia and Coagulation Intravascular Disseminated 62



V. Patil et al.





Table 62.3 ISTH diagnostic




Platelet count



scoring system for DIC

>100 × 109/L




<100 × 109/L




<50 × 109/L




Fibrin marker (e.g., D-dimer, FDP)




No increase




Moderate increase




Strong increase




Prolonged PT




<3 s




>3 but <6 s




>6 s




Fibrinogen level




>1 g/dL




<1 g/dL



D-dimer, FDP, and antithrombin levels can be used for rapid and specific diagnosis of DIC, with antithrombin providing an indicator for severity and prognosis.

Diagnosis of DIC is essentially confirmed by demonstrating increased thrombin generation (decreased fibrinogen) and increased fibrinolysis (elevated D-dimer or FDP).

Step 4: Ascertain severity and prognosticate outcome

Calculate the DIC score (Table 62.3) with the ISTH (International Society of Thrombosis and Haemostasis) scoring system which provides objective measurement of DIC and correlates with outcome.

Step 5: Continue resuscitation

Continue resuscitation and maintain hemodynamic stability using crystalloids and/or colloids.

In colloids, preferably use gelatins as they do not interfere with clotting.

If you are using starches, use tetrastarch preferably, as they have less effect on the coagulation profile, but do not exceed maximum dose (50 mL/kg/day).

Step 6: Correct coagulopathy (see Table 61.2 in Chap. 61)

Repeat the coagulation profile and complete blood count frequently and replace blood and blood products.

In the presence of ongoing blood loss, try to normalize prothrombin time and APTT and aim to maintain platelet count of more than 50,000.

Do not use antifibrinolytic agents as they may aggravate thrombosis.

Patients who have DIC with a primary hyperfibrinolytic state and who have severe bleeding can be treated with lysine analogues, such as tranexamic acid (e.g., 1 g every 8 h).

There is no role of heparin in actively bleeding patients.

62 Disseminated Intravascular Coagulation and Thrombocytopenia




It should be considered only where thrombosis predominates such as arterial or venous thromboembolism or severe purpura fulminans associated with vascular skin infarction.

Step 7: Treat the underlying disorder

Repeat the tests to monitor the dynamically changing scenario and continue treatment based on clinical observation and laboratory results.

Once patient stops bleeding, do not try to correct laboratory abnormalities as transfusion of blood and blood products should be based on clinical condition and bleeding rather than laboratory values only.

Calculate score

More than 5 overt DIC: repeat score daily.

Less than 5 suggestive for nonovert DIC: repeat for the next 1–2 days.


A 50-year-old male patient was admitted with acute pancreatitis. His blood investigations showed Hb 10.7 g%, WBC 12,000/mm3, and platelets 110,000/ mm3. On the third day, he worsened clinically. His WBC count was 20,000/mm3 and platelets were 70,000/mm3. However, the next day, he further deteriorated requiring inotropes and ventilatory support. His Hb dropped to 6.4 g%, WBC count rose to 28,000 mm3, and platelets further dropped to 40,000/mm3.

Step 1: Resuscitate

Resuscitate, monitor, and stabilize in the ICU (refer to Chap. 78). In patients with low platelets and coagulopathy, ultrasound-guided jugular venous catheter insertion for fluid resuscitation should be performed.

Send blood for peripheral blood smear, grouping, cross-matching, coagulation profile, and biochemistry.

Step 2: Assess severity of thrombocytopenia

Thrombocytopenia is defined as a platelet count less than 150 × 109/L.

In critically ill patients, a threshold of less than100 × 109/L may be taken.

The ability to form a hemostatic plug is retained until the platelet count drops to less than 100 × 109/L

Step 3: Assess cause of thrombocytopenia (Table 62.4)

Careful history, physical examination, previous medical records, and current chart review usually reveal the cause of low platelet count.

Ask about bleeding from other sites in past, for example, frequent nosebleeds, gum bleeds, melena, hemoptysis, and blood in stool or urine.


V. Patil et al.


Table 62.4 Causes of thrombocytopenia

Pseudothrombocytopenia seen in

EDTA causes in vitro clumping of platelets. Presence of

asymptomatic patients

platelet clumps in the peripheral smear and a normal repeat


platelet count in citrated blood confirm pseudothrombocy-


topenia. In some patients, automated blood reports show


thrombocytopenia due to presence of giant platelets that are


counted as RBCs in automated machines; however, manual


platelet count is normal

Dilutional thrombocytopenia

Massive blood transfusion

Ambulatory patients



Drug-induced—chemotherapy, miscellaneous drugs


Infections—Epstein–Barr virus (EBV), HIV, others


Connective tissue disorders—rheumatoid arthritis, systemic


lupus erythematosus (SLE), antiphospholipid antibody






Primary marrow disorder

Acutely ill patients







Posttransfusion purpura

Pregnant patient

Gestational (platelet count >70 resolves after pregnancy)




HELLP—hemolysis, elevated liver enzymes, low platelets

Cardiac patients



Cardiac bypass




Gp IIb/IIIa inhibitor-related


TTP related to clopidogrel or ticlopidine

Patient with thrombosis



Antiphospholipid antibody syndrome


Paroxysmal nocturnal hemoglobinuria

History of previous platelet counts.

History of previous blood or platelet transfusion.

Medication history and review medication chart—particularly, use of heparin, warfarin, and antiplatelet agents including nonsteroidal anti-inflammatory drugs (Table 62.5).

Heparin-induced thrombocytopenia (HIT) should be considered if the platelet count decreases by 50% and/or thrombosis occurs 5–14 days after starting heparin.

History of known systemic conditions associated with defects in platelets like alcoholism, cirrhosis, HIV infection, systemic lupus erythematosus (SLE), and uremia.

Family history of excessive bleeding.

62 Disseminated Intravascular Coagulation and Thrombocytopenia





Table 62.5 Drugs associated with thrombocytopenia









Drug-specific antibody


H2 receptor blockers

Ranitidine, cimetidine




Gp IIb/IIIa inhibitors



Drug-dependent antibody


Vancomycin, rifampicin,






chloroquine, amphotericin B,











Aspirin, diclofenac, ibuprofen





Valproate, carbamazepine,
















Quinine, furosemide, thiazide,








Hapten-dependent antibody



Penicillin, some cephalosporins


Induction of autoantibodies







Gold salts









Chemotherapeutic agents






Fluconazole, daptomycin,






ganciclovir, nitrofurantoin,











Digoxin, haloperidol




Gp IIb/IIIa inhibitors



Immune complex with PF4



Unfractionated and low-molecular-





weight heparin


Interference with folate











Thrombotic microangiopathy



Clopidogrel, ticlopidine


Preexisting antibodies






Table 62.6 Factors associated with platelet refractoriness



Nonimmune factors

Clinical factors

Splenomegaly, fever, infection, bleeding, dissemi-





nated intravascular coagulation





Amphotericin B, vancomycin, ciprofloxacin, heparin


Patient factors

previous pregnancies, previous transfusions


Immune factors


HLA, platelet specific, erythrocyte





Length of time the platelets are stored


Perform physical examination to look for:

Evidence of bleeding in skin, mucous membrane, joints, soft tissue



Step 4: Transfuse platelets (Table 62.6)

Three types of platelet products are commonly used in clinical practice:

– Random-donor platelets (RDP)

Table 62.7 Approach for management of thrombocytopenia







ITP, after viral illness, may be

IgG antibodies against platelet antigens, platelet

All ages, common in young adult females

Steroids, prednisolone 1 mg/kg/day

associated with antiphospho

clearance by spleen, inadequate platelet


for 1–2 weeks, taper

lipid antibody syndrome, may

production response

Severe thrombocytopenia with normal

IVIG infusion 1g/kg/day for 2 days

be initial presentation of


RBC and WBC morphology and number


connective tissue disease,


Diagnosis by exclusion

Anti RhD antibodies 50–75 m/kg IV

lymphoploriferative malignancy




(Rh + Ve patients with intact spleen)





-Inherited or acquired deficiency of von

Microangiopathic hemolytic anemia,

FFP transfusions until the patient is


Willebrand factor cleaving protease

thrombocytopenia, renal insufficiency,

ready for plasma exchanges



fever, and mental status changes



Idiopathic or secondary to Escherichia coli

Schistiocytes in peripheral smear, raised

Plasma exchanges


diarrhea, HIV infection, certain drugs

LDH, normal coagulation profile

Platelet transfusions only in


(ticlopidine, clopidogrel, quinine, cyclosporine


life-threatening bleeding


A, mitomycin A, cisplatin, etc.), pregnancy, bone




marrow transplant, and metastatic carcinomas



Drug-induced thrombocytopenia

Antiplatelet agents’ and other drugs’ immune

History—no other blood or coagulation

Stop the offending drug




Supportive care


Chemotherapy and alcohol—directly inhibit

Most chemotherapeutic drugs—nadir of

Supportive care



blood counts in 7–10 days, recovers over




2–3 weeks Nitrosureas and mitomycin




cause prolonged myelosuppression



Heparin—antibodies against heparin–platelet

Type I—modest transient thrombocytopenia

Spontaneous recovery


factor 4 complex

in 2–3 days after heparin therapy




Type II—less common, occurs 4–14 days

Stop heparin



after heparin therapy




ELISA assay for anti-PF 4 antibody,

Doppler to rule out thrombosis



serotonin release assay, platelet aggregation

Use direct thrombin inhibitors




(argatroban, lepirudin) Fondaparinux




should be used with caution




LMWH and UFH should not be used

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