ICU thrombocytopenia management

1. THROMBOCYTOPENIA IN
ICU: TRUE PEARLS OF
WISDOM
Nilesh Wasekar
MD MED
DM Hematology
Consultant HCG Hospital Nashik

2. Hui P, et al. Chest. 2011. 139(2): 271-8.
Williamson DR, et al. Chest. 2013. 144(4): 1207-15.
THROMBOCYTOPENIA IN ICU
• Platelet count < 150,000/L
• The most common hemostatic disorder in
critically ill patients
– Incidence approaches 50%
• Association between thrombocytopenia and
– Mortality
– Poor ICU outcomes

3. MARKER OF ILLNESS AND SEVERITY
• 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

4. Moreau D, et al. Chest. 2007.131(6):1735-41.

5. Acka S, et al. Crit Care Med. 2002. (30)4:753-6.
Shaded = non-survivors White = survivors

6. • Blood loss or
hemodilution
• Decreased production
– Infection
– Toxins (including drugs)
– Inflammatory mediators
– Bone marrow disorders
– Liver disease
MECHANISM
• Increased destruction
– Consumption
– Immune-mediated
• Sequestration
– Spleen
– Liver
– Lungs (ARDS)
• Pseudothrombocyto
penia
Akca S, et al. Crit Care Med. 2002. 30(4): 753-6.
Vanderscheuren S, et al. Crit Care Med. 2000. 28(6): 1871-6.

7. • Infectious
– Sepsis**
– HIV
– HCV
– Other viral infections
• Drug-induced
• Hematologic disease
– TTP/HUS
– ITP
– Bone marrow disorders
– Macrophage activation
syndrome
• Liver disease
• DIC
• Massive transfusion
(dilutional)
• Rheumatologic disease
• Idiopathic/unknown
Lim SY, et al. J Korean Med Sci. 2012. 27:1418-23.
Stasi R. Hematology. 2012. 2012(1):191-7.
DD

8. INITIAL INVESTIGATION
Van der Linden T,et al. Ann Intensive Care. 2012. 2(42).

9. TREATMENT
• Target of treatment is the underlying process
• Supportive care mayinclude
– Platelet transfusion
– Anticoagulation
– Etiology-specific treatments

10. • Is this condition pro-hemorrhagic?
• Is this condition pro-thrombotic?
• Are additional therapies or specialized studies
necessary?
TREATMENT GUIDANCE

11. Decision to transfuse should be based on:
– Platelet count
– Presence of active
bleeding
• Site
• Severity
– Etiology
– Risk of thrombosis
– Risk of hemorrhage
• Platelet function
• Invasive procedures or
surgery
– Associated treatment
Van der Linden T,et al. Ann Intensive Care. 2012. 2(42).
RECOMMENDATIONS FOR TREATMENT

12. PROBLEM
How to evaluate
thrombocytopenia
in ICU
When to evaluate How to treat it

13. WHEN TO EVALUATE
Thrombocytopenia is
defined by a platelet
count (PC) < 150 × 109/L
In intensive care,
pseudothrombocytopenia
should be ruled out
PC < 100 × 109/L or a >
30% decrease in PC

14. QUESTIONS TO ASK WHEN EVALUATING
THROMBOCYTOPENIA IN THE ICU PATIENT
What is the context of the
patient’s ICU admission?
preexisting illness or the use
of a drug
thrombotic thrombocytopenic
purpura, hemophagocytic
syndrome, or acute
leukemia?
Was there major trauma or
surgery

15.  The underlying mechanisms and etiologies of
thrombocytopenia in intensive care are often
multiple
 Sepsis is the main etiology of thrombocytopenia in
intensive care and is usually associated with (DIC)
 The clinical context should suggest the etiology of
thrombocytopenia in most cases in intensive care

16. BMA
 In thrombocytopenia in intensive care, bone marrow
biopsy should not be performed routinely
 can be considered when there is no obvious
etiology or when other cell lineages are affected

17. ANTIPLATELET ANTIBODIES
 Screening for antiplatelet antibodies is unjustified in
the initial diagnostic approach to thrombocytopenia

18. EMERGENCIES WITH THROMBOCYTOPENIA
Thrombotic
microangiopathy
Macrophage
activation
syndrome
Catastrophic
antiphospholipid
syndrome
DIC

19. British Journal of Haematology, Volume: 177, Issue: 1, Pages: 27-38, First published: 16 December 2016, DOI: (10.1111/bjh.14482)
SOME CLUES FOR THE DIAGNOSIS

20.  “History”
 “Comprehensive Approach”
 “Peripheral Smear”
 “Smart Physician”
 “Uncommon presentation of a common disease”
 “Thrombocytopenia in sepsis”

21. “History”

22.  25 years old man
 H/o fever 10 days back
 Received some treatment for fever at hospital
 Platelet count dropped on day 15 of admission

23.  HB 11.0
 Retic 1
 Platelet 25000
 PS Large platelets+
 LDH 400
 DCT negative

24. DRUG INDUCED THROMBOCYTOPENIA

25.  Piperacillin Tazobactum
 Drug stopped and he improved dramatically

26. DRUGS
• Antibiotics
– PCN
– β-lactamase inhibitors
– Carbapenems
– Cephalosporins
– Quinolones
• Anti-epileptics
– Valproate
– Carbamazepine
– Phenobarbital
– Phenytoin
• Alcohol
• Acetaminophen (overdose)
• Anti-platelet agents
• NSAIDs
• Heparin
• H2 blockers
• Chemotherapy
• Herbals
• Snake venom
Lim SY, et al. J Korean Med Sci. 2012. 27:1418-23.
Thiele T, et al. Semin Hematol. 2013. 50(3): 239-50.

27. HIT

28. “Peripheral
smear”

29.  35 years old man
 Came with generalized weakness, jaundice
 Required a transfusion once a day for last 5 days
 Pallor ++
 Spleen JP
 Icterus ++

30.  HB 5.0
 MCV 130
 Retic 15
 LDH 3000
 PS: NCNC(local lab)
 G6pd: Normal
 B12/Iron profile : Normal
 Stool for OB negative

31. PS

32.  DCT was positive 4+

33.  EVANS SYNDROME

34. “Comprehensive Approach”

36. Smart physician

37. • 32 years, 15 days PNC, presented with easy
fatigability, fever, headache, nausea, jaundice
• CBC picture: Hb 7.3 MCV 80 TLC 5000(N78 L22)
Plt 20000/mm3
• PT/APTT Normal
• Billirubin 5 (I: 4) Retic 25 Creatinine 0.9 mg/dl
• Haptoglobin low
• Plasmic score: 7 {High RISK}
37

38. • PS was having :

39.  MAHA/TTP
 ADAMTS 13 was low
 Responded well to TPX

40. SCHISTIOCYTES
0.5% -1% is
suggestive of
disseminated
intravascular
coagulation (DIC)
A count superior
to 1% is typical of
thrombotic
thrombocytopenic
purpura (TTP)
with a common
range of 3–10%,
In healthy
individuals, below
0.5%

41. “UNCOMMON PRESENTATION OF A COMMON
DISEASE”
• 15 years old boy presented with easy fatigability,
jaundice
• Pure vegetarian
• CBC picture: Hb 5 TLC 9000 platelet 35000
• Billirubin 5.0 (I)
• Retic 1
• LDH 5000
• PS: Macro, macroovalo, TD, Polycromasia,
Sperocytes, BS, Schistiocytes

42. 42
B12 levels : 45
B12 deficiency anemia

43. SEVERE B12 DEFICIENCY PRESENTING AS
HEMOLYTIC ANEMIA

44. “Sepsis and
thrombocytopenia”

45.  47 years old lady
 DM
 Burning micturition
 Presented with high grade fever, hypotension,
reduced urine output
 Hb 9.0
 LDH 780
 Retic 1%
 TLC: 25000 (N80 L16 Band 04)
 Platelet : 30000
 Procal : 11

46.  Peripheral smear was normal with few toxic
granulations in the neutrophils.
 Malaria/Dengue Negative

47. • Represents hematologic system dysfunction in
sepsis
• Results from activation of the host inflammatory
response
• Mechanisms of thrombocytopenia in sepsis
– Pseudothrombocytopenia
– Bone marrow suppression
– Non-immune mechanisms
• Consumption
• DIC
– Immune mediated mechanisms
WarkentinTE, et al. Hematology.2003. 2003(1): 497-519.
SEPSIS

48. “TOP 3 OF ICU THROMBOCYTOPENIA”
 HIT
 Drug
 Sepsis

49. WHEN WE TREAT THROMBOCYTOPENIA IN CRITICALLY ILL
PATIENTS?
 The decision to treat thrombocytopenia should be
based on the PC but also on the:
 Presence of active bleeding (type, potential
severity),
 Mechanism of thrombocytopenia (central or
peripheral),
 Etiology,
 Risk of thrombosis,
 Risk of hemorrhage (platelet disorders, invasive
procedures or surgery), and
 Associated treatments (strong agreement).

50. BLEEDING SCORE
 0: no hemorrhage;
 1: slight hemorrhage;
 2: patent blood loss not requiring red cell
transfusion;
 3: blood loss requiring red cell transfusion;
 4: hemorrhage with considerable morbidity

51. PROPHYLACTIC PLATELET TRANSFUSION IS NOT
RECOMMENDED IN THE FOLLOWING SITUATIONS:
 posttransfusion purpura
 thrombotic thrombocytopenic purpura (TTP)
 catastrophic antiphospholipid syndrome
 hemolytic-uremic syndrome (HUS)
 heparin-induced thrombocytopenia (HIT)

52. RECOMMENDED TRIGGERS FOR PLATELET
TRANSFUSION IN CRITICALLY ILL PATIENTS
Transfusion indication Threshold platelet count (×109/L)
Prophylactic transfusion of adult patients 10
Before central vein catheter placement 20
Before elective diagnostic lumbar
punction
50
Urgent diagnostic lumbar puncture 20
Before major elective surgery (excluding
neurosurgery)
50
Prophylactic transfusion of
nonthrombocytopenic patients before
cardiopulmonary bypass surgery
No transfusion (only in case of bleeding)
Patients with intracranial hemorrhage and
antiplatelet drugs
No platelet transfusion

53. ROLE OF TPO AGONIST IN SEPSIS RELATED
TCP
 No prospective study
 One case series showing some benefit
(eltrombopag)
 Can be useful in setting of the refractory immune
TCP where primary treatment with
immunosupressansts fails

54. ROLE OF STEROIDS/IVIG
 Use of immunoglobulins in thrombocytopenic
patients with sepsis is not recommended
 In very severe forms (PC < 5 × 109/L or with life-
threatening bleeding) of drug-induced
thrombocytopenia with an immune mechanism,
intravenous immunoglobulins or even
plasmapheresis is possible
 Post transfusion purpura can be treated with IVIG
 Steroids not advisable in sepsis, useful in immune
causes and TTP

55. MANAGEMENT OF ANTICOAGULATION IN TCP
(LMWH) should probably be
prescribed routinely in all adult
patients admitted to intensive
care, except when the PC <
30 × 109/L or there is a major
risk of hemorrhage
Any interruption of antiplatelet
drugs in an intensive care
patient should be as short as
possible, especially if the patient
has a drug-eluting stent
When a patient admitted to
intensive care is already taking
antiplatelet drugs, these should
probably be withdrawn if there is
a risk of hemorrhage (PC <
50 × 109/L)

56. SUMMARY
• Certain features of thrombocytopenia should prompt
investigation
– < 100,000 or decrease > 30%
– Rapid decline
– Failure to rebound after 5-7 days
– Decline after initial recovery
• Initial investigation should include peripheral smear and
other labs as clinically indicated
• Decision to transfuse depends on platelet count, etiology,
bleeding risk, thrombotic risk, other factors
• Consider anticoagulation and other etiology-specific
treatments depending on clinical scenario

57. Thank you