Perioperative thrombocytopenia:

evidence, evaluation, and

emerging therapies
A. Nagrebetsky, H. Al-Samkari, N. M. Davis, D. J. Kuter and J. P. Wiener-Kronish

Efriko Septananda Saifillah

PEMBIMBING:
dr. Herwindo, SpPD
 BACKGROUND
•Thrombocytopenia  platelet count below 150 x 109 L  5 – 10% patients
perioperative
•platelet count is relatively stable over the lifetime of an individual
• change in platelet count  suggestive of an alteration in normal physiology
•Large observational study relationship between preoperative thrombocytopenia
and 30-day mortality
•101-150 x 10^9 : 30% higher likelihood of death
•100 x 10^9: more likely have sepsis, renal complications, adverse pulmo
outcome
•platelets are involved not only in haemostasis, but also in inflammatory and immune
responses and wound healing.
 Thrombocytopenia and the risk of
bleeding
• mild (100-149 x 10^9 /L), moderate (50-99 x 10^9 /L), and severe (<50x 10^9 /L)
• relationship between platelet count and bleeding risk is not linear and depends on platelet function
and other patient-specific variables
• platelet counts above 10x 10^9 /L  sufficient to allow for normal thrombin generation
• WHO bleeding scale classifies bleeding :
•Grade 0 (no bleeding),
•Grade 1 (minimal bleeding, such as petechiae),
• Grade 2 (mild blood loss, such as visible blood in stool or urine),
•Grade 3 (gross blood loss, such as profuse GI bleeding or minor intracerebral haemorrhage),
• and Grade 4 (debilitating, life-threatening bleeding).
• many other factors affect likelihood of bleeding (age, etiology)
THROMBOCYTOPENIA AND
PROCEDURES
•acceptable platelet
counts and indications for
platelet transfusions in
thrombocytopenic
patients undergoing
invasive procedures

•Nearly all studies are

retrospective and
observational.
NON CARDIAC SURGERY
•Preoperative platelet transfusion :
•did not improve patient outcomes or decrease perioperative red blood cell
(RBC) requirements
•higher ASA physical status, lower baseline haemoglobin concentrations
and platelet counts, higher rates of postoperative ICU admission, and a
longer hospital stay
•associated with postoperative mortality
•Thrombocytopenia  a probable marker of intraoperative pathophysiologic
perturbations, was also associated with surgical complications, graft
dysfunction, and sepsis.

Warner MA, Jia Q, Clifford L, et al. Preoperative platelet transfusions and perioperative red blood cell requirements in patients with
thrombocytopenia undergoing noncardiac surgery. Transfusion 2016; 56: 682e90
INTERVENTIONAL RADIOLOGY PROCEDURES
• large single-centre retrospective study ---prophylactic platelet transfusions in patients undergoing interventional
radiology procedures.
 Prophylactic platelet transfusions did not reduce bleeding or improve clinical outcomes when utilised for
patients with counts >50 x 10^9
platelet counts 50x 10^9 L, prophylactic platelet transfusions did not reduce the frequency
of RBC transfusion.

ACUTE ABDOMINAL COMPLICATIONS IN THROMBOCYTOPENIC PATIENTS

• 58 haematologic malignancy patients undergoing emergency abdominal surgery  intraoperative
thrombocytopenia was not associated with prognosis;
THROMBOCYTOPENIA AND THE AIRWAY
It is likely that severe thrombocytopenia increases the risk of bleeding with airway manipulation,
British Thoracic Society Guidelines suggest that bronchoscopy with lavage can be safely performed at platelet counts
>20x10^ 9

Du Rand IA, Blaikley J, Booton R, et al. British thoracic society guideline for diagnostic flexible bronchoscopy
in adults: Accredited by NICE. Thorax 2013; 68: i1e44
Qualitative platelet
dysfunction and procedures
 Acquired platelet dysfunction
•secondary to uraemia, cardiopulmonary bypass, and medications  common in surgical
patients
•aspirin, the non-aspirin NSAIDs, P2Y12 adenosine diphosphate receptor antagonists
(ticlopidine, clopidogrel, prasugrel, ticagrelor, and cangrelor), dipyridamole, and glycoprotein
IIb/IIIa antagonists (abciximab, eptifibatide, and tirofiban).
•long-accepted notion  patients on aspirin presenting with cerebral haemorrhage benefit
from platelet transfusion.
•Study: more serious adverse events (e.g. enlargement of intracerebral haemorrhage or
infections) in the patients who received platelet transfusions (42% compared with 29%
receiving standard care).

•This study concluded that platelet transfusion may be deleterious for this patient population
•Treatment: alternative to platelet tranfussion
 Inherited platelet disorders
•may result in qualitative platelet dysfunction, varying degrees of
thrombocytopenia, or both
•clinical spectrum of bleeding  highly variable
•Excessive bleeding risk in Bernard-Soulier syndrome (def glycoprotein Ib),
autosomal variant Glanzmann thrombasthenia, and Hermansky-Pudlak
syndrome

•Bleeding was twice as common in inherited platelet function disorders

(24.8% of procedures) ---- compared with inherited thrombocytopenias
(13.4% of procedures).
• bleeding was infrequent until platelet count was below 68 x 10^9

Orsini S, Noris P, Bury L, et al. Bleeding risk of surgery and its prevention in patients with inherited platelet disorders.
Haematologica 2017; 102: 1192e203
Evaluation of thrombocytopenia in
the perioperative patient
What to evaluate..?
•haematologic history, including prior platelet count trends and
analysis of any prior thrombocytopenic episodes
•Exacting medication history
•mild thrombocytopenia of known aetiology  proceed to surgery
without additional perioperative workup
•unclear aetiology, severe thrombocytopenia, or unexpected bleeding
 haematology consultation
•following discussion focuses on the causes of unexplained
thrombocytopenia in the postoperative patient,
1. Artifactual thrombocytopenia
1st step – assessment 0f thrombocytopenic postoperative patient
(mostly dt platelet clumping – 0.1 %) – dt insignificant antibodies?
 performing an automated platelet count from patient
blood in a citrated or heparinised tube instead of an EDTA
2. Non-artifactual thrombocytopenia in the postoperative
patient

•Examination of the peripheral blood film often suggestive or diagnostic

•If platelet transfusion occured  post-transfusion platelet count should always be
obtained within 30 min after episode (calculation of the corrected count increment
(CCI). )
•if falure CCI : valuable diagnostic information, such as the presence of antiplatelet
antibodies
• Can also be suggestive by history alone ( large quantities of iv fluids/ massive PRC tranfusion – dilutional
thrombocytopenia)
• Infection or sepsis-- precipitous decreases in the platelet count over a short period of time
 DIC, secretion of neuraminidase by certain bacteria, medications (vide infra) administered to treat
infection
 Ddimer measurement -- little utility in the postoperative patient
DRUG INDUCED THROMBOCYTOPENIA
 most common : heparin and antibiotics ( most common amiodarone, ampicillin, haloperidol,
ibuprofen, naproxen, piperacillin, ranitidine, trimethoprim-sulfamethoxazole, and vancomycin)
 if platelet count still high enough  moitored over the vourse of treatment
If it decreased to the point that bleeding concern  should be discontinued, if possible
Heparin-induced thrombocytopenia
•up to 2.5% of inpatients receiving heparin and is most common in surgical patients
(mostly major trauma or major surgery).
•immunologic recognition of heparin-platelet factor 4 (PF4) complexes 5-10 days after
heparin initiation, resulting in platelet activation, thrombocytopenia, and high
thrombotic risk
•Incidence of venous thromboembolism is 17.55%, incidence of arterial thrombosis is
3x10%, and mortality is 5e10% in patients
•Must be distinguished with Heparin Associated Thrombocytopenia (HAT) 
thrombocytopenia after beginning of heparin
Alternatives to platelet transfusion in
the thrombocytopenic surgical patient
the only currently available therapy capable of achieving a
rapid, generally predictable increase in platelet count,
has several risks: Tranfusion reaction, highest risk of
bacterial sepsis of any blood product.
 proper alternatives to platelet transfusion should always
be considered in the thrombocytopenic surgical patient.
Desmopressin
•rapid-acting vasopressin analogue that acts principally by inducing the
release of large von Willebrand factor  increased circulating von
Willebrand factor could theoretically improve platelet adhesion to the
endothelial surface

•a non-specific haemostatic agent in thrombocytopenic surgical patients

who are uremic or refractory to platelet transfusions
•Well tolerated, with hyponatremia being the most common adverse
effect.
Antifibrinolytic agents
•non-specific haemostatic agents via competitive inhibition of
plasminogen, blocking its binding to fibrin strands and reducing clot
lysis
•mostly used outside the thrombocytopenic setting to promote
haemostasis mucocutaneus bleeding and perioperative )
•Efficacy was shown in non-thrombocytopenic patients undergoing
open cardiac surgery, orthopaedic surgery
•reasonable to consider a trial of antifibrinolytic therapy in a
thrombocytopenic patient refractory to platelet transfusion or for
whom platelet transfusion is not acceptable
Procoagulant bypass agents
•widely used to achieve haemostasis in patients with haemophilia and
factor inhibitors
•Cochrane analysis (rFVIIa use for the prevention and treatment of
bleeding outside of the haemophilia )
 decreased red cell transfusion requirements and decreased blood
loss, but no evidence of mortality benefit and an increase in arterial
thromboembolic events
TPO receptor agonists
•bone marrow megakaryocytes and megakaryocyte progenitors to increase
platelet production
•Increase approximately 5-7 days after administration of a TPO receptor
agonist and peaks 10- 14 days later
•Retrospective cohort study: high efficacious ( 47 x 10^9 increased to 164 x
10^9
• in chronic liver disease  attractive prospect because of TPO deficiency
• effective in reducing platelet transfusions and bleeding, but the study was
terminated early because of increased incidence of portal venous
thrombosis in the eltrombopag arm.
Raising the haematocrit

•Haemostasis is improved in renal failure patients by increasing the

haematocrit through transfusion or erythropoietin treatment.

•higher RBC mass (which flows in the centre of the blood vessel) ‘pushes’
platelets closer to the endothelial cell wall, thereby increasing the
haemostatic effect
conclusion
The bleeding risk in thrombocytopenic patients undergoing
surgical procedures is difficult to predict
Recommendations for procedure-specific ‘safe’ platelet counts often
lack a robust evidence base
true magnitude of benefit ofprophylactic platelet transfusion remains
unclear and the need for platelet transfusion should be assessed on a
patient by-patient basis.
haematology consultation may behelpful in diagnosing the aetiology of
thrombocytopenia,
Thank you