Thrombocytopenia is one of important predictor of poor prognosis in ICU patients, how to deal and proper management.

1. Thrombocytopenia in ICU
Marwa Abo Elmaaty Besar
Lecturer Of Internal Medicine
(Rheumatology Immunology Unit)
Mansoura University

2. Agenda:-
• Epidemiology.
• Causes and differential diagnosis.
• Approach to thrombocytopenia in ICU.
• Treatment.

3. Thrombocytopenia in ICU:
• Definition; platelet count <150,000/L, ,100,000/L, and sometimes ,50,000/L).
• Degrees of thrombocytopenia can be subdivided into
• Mild (platelet count 100,000 to150,000/microl),
• Moderate (50,000 to 99,000/microl),
• Severe (<50,000/microl)
Brogly N, etal 2007

4. Epidemiology thrombocytopenia in ICU:-
• Thrombocytopenia is very common in critically ill treated in the intensive care unit
(ICU).
• Frequency :-
• 35% to 45% of ICU patients, with a somewhat 5% to 20% for severe
thrombocytopenia.
• Surgical ICU patients have a higher incidence of severe thrombocytopenia,
compared with medical ICU.
Vanderschueren S, etal 2000

5. The dynamics of platelet counts in ICU patients
Crowther MA, etal 2005

6. Selleng S, etal 2010

7. Common causes of Thrombocytopenia in
ICU

8. Drug-related thrombocytopenia
• Is a relatively common cause of thrombocytopenia in ICU patients.
• Drug-induced nonimmune thrombocytopenia (DTP) majority of cases, except for HIT,
 Such as histamine H2 antagonists, nonsteroidal anti-inflammatory drugs.
 Due to toxic bone marrow suppression.
• Drug-induced immune thrombocytopenia(DITP) is much less frequent than DTP,
 Such as glycoprotein IIb/IIIa inhibitors, trimethoprim/sulfamethoxazole, Antibiotics, Antiepileptic.
 Begins 5 to 14 days after starting a new drug.
 Present with abrupt platelet count fall within 1 to 2 days,
 Platelet a nadir below 20* 109 /L, always accompanied by mucocutaneous bleeding.
• Laboratory tests for the detection of drug-dependent antiplatelet antibodies, usually not available.
• The clinical relevance of laboratory testing for DITP antibodies is twofold.
 First, it allows objective confirmation of an adverse drug effect (relevant for pharmacovigilance).
 Second, it is important for the individual patient (future drug avoidance).

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10. Thrombocytopenia in patients have sepsis:-
• Venkata et al, 2013; Sepsis or SIRS is the commonest cause of thrombocytopenia in ICU with the
severity and incidence greater than septic shock.
• Larkin et al, 2016; The explanation is multifactorial;
1. Platelet binding to the endothelium, leucocyte-platelet aggregate formation,
2. Immune-mediated mechanisms,
3. Haemophagocytosis, bone marrow suppression,
4. Complement activation and in patients with overt DIC
• Thachil, 2016;
• If the platelet counts worsen despite appropriate antibiotics along with other laboratory markers, this
would suggest the development of DIC and the need for additional interventions.
• If the platelet counts are stable or improving, surrogate marker for improvement from sepsis.

11. Heparin-induced thrombocytopenia (HIT):-
• HIT is immune mediated, usually occurs 5 to 14 days after starting heparin, platelets fall below
20* 109 /L
• HIT is both over and under-diagnosed in the ITU.
• Incidence of “true” HIT <1% in the ICU population despite that majority exposed to heparin.
• Mechanism; Formation of antibodies against PF4-heparin complexes lead to activation of platelets
• Rapid-onset HIT within hours in preimmunized patients appeared unlikely, as the platelet count
started to decrease after day 2 only.
• Warkentin 2006;
 Thrombosis that begins >5 days after receiving heparin should consideration HIT.
 Thrombosis presenting feature 1/5 HIT patients with thrombocytopenia becoming apparent only over the
ensuing days.
 Hypotension in HIT patients in ICU should prompt consideration of acute adrenal failure
BLOOD, 29 DECEMBER 2016 x VOLUME 128, NUMBER

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13. Prognostic significance of
Thrombocytopenia in ICU

14. Thrombocytopenia as a prognostic marker:-
• Nearly all studies (2000-2010) found an inverse correlation of the platelet count with
the risks for a prolonged ICU stay and mortality (mortality rate 31%–46% in
thrombocytopenic patients vs 16%–20% nonthrombocytopenic patients).
• Patients with thrombocytopenia have:
–Higher admission APACHE II, SAPS II, MODS II scores
–Higher mortality within the same APACHE II or SAPS II quartiles
–Higher ICU (39% vs. 24%, p<0.0005) and hospital (56% vs 48%, p<0.0005)
mortality
–Longer duration of mechanical ventilation (11 vs. 5 days, p<0.0005)
–Receive more PRBC, FFP, platelet transfusions

15. Thrombocytopenia as a risk for organ impairment:-
• Thrombocytopenia in critical ill patients as the surrogate marker for development of
organ failure and vascular leakage.
• Detailed, prospective studies stated that a gradual decline in platelet count may be
considered an early marker of complications ;
 Renal failure,
 Acute lung injury(ALI)/respiratory distress syndrome
 Vascular leakage syndromes.
• Mechanism: Platelet aggregation and adhesion to the endothelium, circulating platelet-
leucocyte aggregates, as well as DIC-associated fibrin deposition, can lead to
microvascular ischaemia, which can manifest as organ failure.
Thachil, 2015, Nurden, 2011

16. When To Worry About Bleeding
• The concept of a "safe" platelet count is imprecise,
• Bleeding is a concern in patients with severe thrombocytopenia; however, the correlation between
platelet count and bleeding risk is uncertain.
• Severe spontaneous bleeding is rare; it is most likely with platelet counts <20,000/microL,especially
<10,000/microL.
• Surgical bleeding with platelet counts <50,000/microL(<100,000/microL for some high-risk procedures as
neurosurgery or major cardiac, orthopaedic surgery).
• Bleeding risk in ITP may be slightly less than that in other conditions (ITP with platelet count of
30,000/microL than we are about bleeding in an individual with aplastic anemia and a platelet count of
30,000/microL).
• Clinical predictors of bleeding:-
 Prior bleeding episodes.
 The presence of wet purpura.
 Possibly haematuria.

17. Approach of Thrombocytopenia in
ICU

18. Approach thrombocytopenia in ICU Patients

20. Management of Thrombocytopenia in ICU:
• Specific management of the causative condition should result in improvement of the platelet
counts.
• The fact that severe thrombocytopenia lead to bleeding so platelet transfusions may be
indicated.
Antithrombotic therapy should be considered in thrombocytopenia associated with organ
impairment.
Thrombocytopenia in patients confirmed to have sepsis ; Supportive treatment with focus
on fully treating the septic episode is the key.
HIT; substitution by non heparin
Drug induced thrombocytopenia; cessation of the drug sufficient with rapid recovery of
the platelet count.

21. Platelet count thresholds for
transfusions
Stanworth et al (2013)
• Liebermanet al, 2014 and Kumar et al, 2015; Different guidelines recommend platelet transfusion
thresholds largely based on expert opinion.
• Further studies to assess the bleeding risk from low platelet count using methods like thrombin
generation tests and possibly platelet-related thromboelastography methods.
• Platelet transfusions in TMA or HIT should be avoid unless there is perceived risk of life-
threatening haemorrhage in these situations.
• Squizzato et al, 2016; The most accepted platelet count threshold for transfusions are
 A level of 10*109/l for those without risk factor.
 Level of 20–30*109/l for those with additional risk factors for bleeding, such as concomitant
coagulopathy (DIC) or severe hepatic or renal dysfunction
 If platelet dysfunction is a possibility, a higher threshold of 50 *109/l should be considered.
 If neurological complications like intra-cranial bleed, a threshold of 100 * 109 /l has been
suggested.

22. The management of thrombocytopenia in the critically-
ill.
British Journal of Haematology, 2017, 177, 27–38

23. Antithrombotic therapy in thrombocytopenia
associated with organ impairment:-
• Antithrombotic therapy if signs of microvascular impairment:-
1. Acral limb ischaemia,
2. Renal impairment,
3. Cerebrovascular signs or
• ALI in the days following a marked drop in the platelet count,
• The choice of agent is a prophylactic dose of anticoagulant drug like low molecular
weight heparin (LMWH).
• Close supervision will be maintained to detect any bleeding early in such cases
• Avoid giving anticoagulation if the platelet count is <25* 109 /l unless there is evidence
of a macrovascular thrombus (DVT) or microvascular thrombosis (symmetrical
peripheral gangrene).

24. Thrombosis in the thrombocytopenic patient
• Management is a difficult dilemma.
• Firstly, it is important to rule out serious conditions (e.g. HIT, APS, DIC).
• If these are excluded, it safe to therapeutically anticoagulated if the platelet count is above 50 * 109 /l.
• But if platelet count 30–50 *109 /l, unfractionated heparin as the anticoagulant of choice.
• If the count is less than 30 * 109 /l,
• Anticoagulation is not administered or given at a reduced dose
• Mechanical thromboprophylaxis is ensured.
• Any thrombotic risk factors (e.g. removal of central lines) are addressed.
• In all these cases,
• Detailed shared discussions with the family about the high-risk situation.
• Platelet counts are monitored closely to safely initiate or stop anticoagulation.

25. Antiplatelet therapy for sepsis in ICU:
• Boyle et al, 2015, Winning et al, 2010; Harr et al, 2013; Valerio-Rojas et al, 2013;
ITU patients who were on antiplatelet therapy have better survival and
interestingly lesser risk of developing ALI and multi-organ failure and lesser risk of
mortality
• Jecko Thachil etal2017, Theodore E etal 2017. advise not routinely use aspirin or
antiplatelet therapy in these cases unless on a trial basis.
• Finally; it would continue the antiplatelet agent if the patients were already
receiving it and has not acquired a heightened bleeding risk in the ITU up to a
platelet count threshold of 25 * 109 /l.

26. Management of HIT:
• Treatment; substituting heparin with an alternative (non heparin) anticoagulant.
• Platelet count monitoring every 2 or 3 days from day 4 to day 14.
• Patients should be
 Therapeutically anticoagulated for 3 months after HIT with a thrombotic complication
 For 4 weeks following HIT without a thrombotic complication.
• Antibodies usually disappear 50 to 80 days after the acute episode of HIT.
• Platelets should not be given for prophylaxis but may be used in the event of
bleeding,

27. Drug induced thrombocytopenia
• Cessation of the drug sufficient to rapid recover in most cases.
• If a patient with DITP develops major bleeding symptoms,
IVIG (1 g/kg body weight on 2 consecutive days) is recommended.
Corticosteroids, however, are usually ineffective.
In case of life threatening bleeding, transfusion of platelet concentrates.
American Society of Hematology, 2017

28. Take home message:-
• Thrombocytopenia in the ICU is common, and correlates with an adverse prognosis.
• It is a sensitive marker for the severity of the disease and associated with increased
mortality.
• Identifying the underlying cause is essential for successful treatment.
• Multiple mechanisms may contribute to thrombocytopenia, and differentiating the
pertinent cause (or causes) in individual patients is challenging.
• A detailed history and careful physical examination are keys to achieving the right
diagnosis, supported by a few laboratory test results.
• Platelet transfusions can be helpful in situations of platelet loss and/or consumption,
but might be deleterious in patients with increased intravascular platelet activation.

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