Bleeding patient in ICU

1. Bleeding patients in ICU
Désirée Coen Herak, PhD
European Specialist of Laboratory Medicine
Department of Laboratory Diagnostics
University Hospital Centre Zagreb

2. TO BLEED OR NOT TO BLEED?
Is the patient at increased
risk of bleeding because of
a congenital or acquired
coagulation disorder?
What is the cause of haemorrhage
during or after surgery?
PREOPERATIVE PHASE INTRAOPERATIVE AND POSTOPERATIVE
A positive bleeding history -
further investigation required,
if necessary, specific coagulation
management established.
Why is the patient bleeding?

3. Diagnostic approach to the bleeding patient
Lang  von Depka Hamostaseologie 2006; 26: S21-S29.
Emergency hemostasis testing is tipically
used to determine which blood products
are needed to correct hemostatic defects
associated with bleeding.
The only successful approach is to try
to establish the underlying pathology
by analyzing the in vivo coagulation
with appropriate assays.

4. VISCOELASTIC GLOBAL HEMOSTASIS TESTS
Lang  von Depka Hamostaseologie 2006; 26: S21-S29.
Viscoelastic assays
(ROTEM and TEG)
can be used for
rapid assessments
of the overall
coagulation status
of the patient.
The gold standard for the diagnosis of HYPERFIBRINOLYSIS or
premature clot lysis, as currently is the only method that can
detect SEVERE FIBRINOLYSIS.

5. Use of ROTEM in predicting postpartum hemorrhage
Collins PW. Blood 2014; 124: 1727-36.
FIBTEM is a rapidly available
early biomarker for progression
of postpartum hemorrhage.

6. FIBTEM  Fibrinogen
Caveat - high
platelet
number
Dangerous to perform ROTEM without a blood count
Lang  von Depka Hamostaseologie 2006; 26: S21-S29.
FIBTEM – INDIRECT METHOD, pharmacological inactivation of
platelets using cytochalasin D
• represents the strength of the fibrin clot without the effect of
platelets
• used in conjunction with EXTEM reagent and compared to EXTEM
analysis allows qualitative analysis of the fibrinogen contribution to
clot strength independent of platelets

7. Srivastava A  KelleherLang A. Continuing Education in Anaesthesia, Critical Care & Pain 2013; 13 Numb. I
ROTEM
STRENTGH LIMITATIONS
Analyze all 3 phases of
coagulation
Preoperative ROTEM results are poor predictors of
postoperative bleeding.
Provide a rapid assessment of
the overall coagulation status of
the patient
Cannot reflect the contribution of endothelium to
coagulation – disorders of primary haemostasis (VWD)
cannot be determined
To be of benefit in detecting a
hypercoagulable state in
postoperative patients
Tracings insensitive to ASPIRIN and CLOPIDOGREL
ROTEM-based transfusion
algorithms reduce rates of
transfusion of blood components
and reduce rates of surgical re-
exploration
Not reflect the effects of hypothermia as the
measurement is undertaken at 37 C.
INTEM cartridges – very sensitive
to residual heparin (0.005
IU/mL), may be useful in
detection of Inadequate heparin
reversal or heparin rebound
Not yet standardized: sample collection and processing
(native or citrated, time delay), activators used and other
modifications, difficult to compare results between
institutions.
Concerns about adequate maintenance, quality control,
and supervision of personnel running the tests

8. Limitations of ROTEM
Lang  von Depka Hamostaseologie 2006; 26: S21-S29.

9. Light transmission platelet aggregation
PLATELET AGGREGATION
• Gold standard for the detection of
hereditary platelet function defects
Disadvantages:
• large sample volume, complex
sample and reagent preparation
• highly labor-intensive and
technically skilled
• time-consuming, not suitable for
emargency testing
• results questionable if Plt count in
PRP < 100 x 109/L
• not useful in predicting bleeding risk
before or during surgery
Jackson SP. Blood 2007; 109: 5087-95.

10. Platelet Function Analyzer (PFA)
STRENTGH
• CTs are not influenced by heparin (unless very high), nor by vitamin K
antagonist therapy or by direct oral anticoagulants
LIMITATIONS:
• Blood collected into sodium citrate anticoagulant - quickly transportation
at ambient temperature avoiding use of refrigeration or pneumatic tube
systems, test have to be completed within 5 hours of collection.
• influenced by thrombocytopenia (<50x109/L) and anaemia (hematocrit
<0.25 L/L)
• not useful for assessing secondary hemostasis (hypofibrinogenaemia,
dysfibrinogenaemia, hemophilia)
• not sensitive to vascular function
PFA-100
INNOVANCE
PFA-200
Favaloro EJ. Am J Hematol 2017; 92: 398–404.

11. NORMAL
1. SEVERE VWD, SEVERE PLATELET
DYSFUNCTION and SEVERE
DRUG EFFECT EXCLUDED
2. IF INITIAL SUSPICION STRONG
CONSIDER testing for VWD,
FULL AGREGATION STUDIES
PFA-100/200 screen (COL/EPI CT)
PROLONGED
COL/ADP CT
NORMAL
CONSIDER/CHECK:
1. DRUG (ASPIRIN?) EFFECT
2. MILD THROMBOCYTOPENIA
3. LOW HAEMATOCRIT
4. MILD VWD
5. MILD PLATELET DYSFUNCTION
PROLONGED
CONSIDER/CHECK:
1. DRUG EFFECT
2. SEVERE THROMBOCYTOPENIA
3. VERY LOW HAEMATOCRIT
4. SEVERE VWD
5. SEVERE PLATELET DYSFUNCTION
Favaloro EJ. Am J Hematol 2017; 92: 398–404.

12. Prolonged COL/EPI CT &
Normal COL/ADP CT
Consider:
• drug effect (aspirin)
• low haematocrit
• mild thrombocytopenia
• mild VWD
• mild platelet dysfunction
Prolonged COL/EPI CT &
Prolonged COL/ADP CT
Consider:
• drug effect
• very low haematocrit
• severe thrombocytopenia
• severe VWD
• severe platelet dysfunction
Normal COL/EPI CT &
Normal COL/ADP CT
Normal result:
• no evident drug effect
• severe thrombocytopenia excluded
• severe VWD excluded
• severe platelet dysfunction excluded
Normal COL/EPI CT &
Prolonged COL/ADP CT
RARE EVENT
PROLONGED
PROLONGEDNORMAL
NORMALCOL/EPI CT
COL/ADP CT
Favaloro EJ. Am J Hematol 2017; 92: 398–404.

13. Sensitivity of PFA-100 for laboratory diagnosis of VWD
VWF:RCo or
VWF:Ag 50%
N=145
VWF:RCo or
VWF:Ag <50%
N=56

14. Acquired von Willebrand syndrome (AWS)
AWS is a rare, but also significantly under-recognized bleeding disorder
occurring in several different clinical situations.
Branchford BR  Di Paola J. Hematology 2012; 2012: 161-167.
AWS – accounts for 22% of patients with abnormal VWF
(Budde et al. Expert Rev Hematol 2015; 8: 799-818.)
Anesth Analg 2012; 114: 73-81.
Diagnostic approach to AWS remains a challenge to the practicing
physician because of the variable clinical presentation and the many
different tests that have to be obtained to prove or rule out the
diagnosis.

15. Acquired von Willebrand syndrome (AWS)
Lison et al. Anesth Analg 2012; 114: 73-81.
VWF is synthesized normally, but
removed from the circulation more
rapidly than expected as a result:
VWF binding to malignant cells
(lymphoproliferative disorders
or Wilms tumor)
Specific or nonspecific
autoantibodies against
VWF and immune
complex formation
(hypothyroidism)
Increased proteolytic activity of high-
molecular-weight multimers under high
shear-stress conditions
(congenital heart disease, aortic stenosis
and angiodysplasia)

16. Tiede A et al. Blood 2011;117:6777-85.
Pathways to diagnose AWS according to the reason of testing
The same routine VWF tests are in use for VWD and AWS diagnosis.
NONE OF THESE TESTS IS ABLE TO DIFFERENTIATE BETWEEN VWD AND AWS

17. Lippi G, Favaloro EJ, Franchini M . Semin Thromb
Haemost 2009; 35: