s1643 your turn: management of the bleeding patient · coagulation factor xa, inactivated-zhzo 28...

S1643 Your Turn: Management of the

Bleeding Patient

Thomas DeLoughery, MD

Theresa A. Nester, MD, FCAP

© 2018 College of American Pathologists. Materials are used with the permission of the faculty.

Objectives

2

• Act as a transfusion medicine consultant for an

actively bleeding patient

• Educate pathologists on the reversal of new

anticoagulant agents and recent platelet

transfusion guidelines

• Help develop protocols for patients who are on

warfarin and are experiencing intracranial

hemorrhage


Case 1

3

A 68 year old woman has sustained a hip fracture after

falling off her horse.

• The patient takes warfarin for atrial fibrillation.

• Current INR is 3.5. Other coagulation tests are

normal. Hemoglobin = 8.5 g/dL.


Vitamin K

• Both oral and IV very effective

− PO "targeted" to liver

− IV faster

• Sub-q and IM not effective in RCT and should not be used!

• Slow infusions of diluted vitamin K has very low incidence

of anaphylaxis – 50ml over 20 minutes

• No "rebound" with reversal

4© 2018 College of American Pathologists. Materials are used with the permission of the faculty.

5.8

2.9

6.2

4.2


Routes of Vitamin K

6

Route Initial INR 24hr INR

LDIV 11.9 3.2

HDIV 13.9 2.8

SC 14.9 4.9

PO 9.4 2.4


Oral

IV


FACTOR IN VIVO ½ LIFE % NEEDED FOR

HEMOSTASIS I 3-6 Days 12 - 50 II 2-5 Days 10 - 25 V 5- 36 Hours 10 - 30 VII 2 –5 Hours > 10 VIII 8 – 12 Hours 30 - 40 IX 18 – 24 Hours 15 - 40 X 20 - 42 Hours 10 - 40 XI 40 – 80 Hours 20 - 30

XIII 12 Days < 5

FACTOR HALF LIVES


Plasma for Warfarin Reversal

• FFP contains all plasma coagulation proteins including the

vitamin K dependent ones (2, 7, 9, 10)

− Factor VII with shortest half-life ~ 3-6 hours

• 1 unit FFP raises factors ~ 5%

• Dose is 15 mls of plasma/kg


Case 2

10

A 74 year old man on warfarin following a left lower

leg deep vein thrombosis has tripped off of a curb 20

minutes ago. He now complains of headache. Head

CT shows an acute subdural hematoma.

INR = 3.5


Kcentra®- a 4 factor prothrombin complex

concentrate (PCC)

11

For patients with a history of warfarin usage presenting with life-threatening bleeding the following is recommended:

1. Give vitamin K 10mg IV over 15-30 minutes

2. If INR is ≥ 1.5 - < 4.0, infuse 25 IU/kg (+/- 10%) Kcentra.

3. If INR is 4.0 - 6.0, infuse 35 IU/kg (+/- 10%) Kcentra.

4. If INR is >6.0, infuse 50 IU/kg (+/- 10%) Kcentra.

NOTE: USE GREAT CAUTION IF PATIENT HAS HAD

THROMBOTIC EVENT IN LAST 3 MONTHS.


Take Home Point:

When using a 4-factor Prothrombin complex

concentrate to reverse the effect of warfarin,

plasma should not be needed.

But do administer IV

vitamin K!

IV vitamin K will

have effect in 4-6

hours.


3- factor PCCs are also available

14

Brand names: Bebulin®, Profilnine®

These contain factors II, IX, and X but not much

factor VII.

Therefore, if this concentrate is used off-label,

a small amount of plasma is still needed to

achieve reversal.


Case 3

15

A 65 year old man on Dabigatran due to atrial

fibrillation presents with a perforated gastric

ulcer. Urgent surgery is required.


Direct Oral Anticoagulant (DOAC) Monitoring

• Increasing use of DOAC in population

• Not required for routine use

• Can be use to assess

− Compliance

− Need for reversal

− Presurgerical

• Routine tests variably effected by drugs


Routine Tests

• Dabigatran – PTT

− Thrombin time more sensitive

• Rivaroxaban – INR

− Anti-Xa more sensitive

• Apixaban – Ø


• Edoxaban – INR


• For life threatening bleeding treat without waiting for levels


DOAC Reversal

• Specific reversal agent available for

Dabigatran

• Idarucizimab

• Coagulation factor Xa (recombinant),

inactivated-zhzo


Dabigatran Reversal


Idarucizumab


Clinical use of Idarucizumab

• Effective in ~ 98% of patients in reversing

thrombin and Ecarin time

• 98% of patients could undergo emergency

surgery

• ~ 2% of patients required redosing for

bleeding

• 30 day thrombosis seen in ~ 5% patients

21

N Engl J Med 2017


Conclusion

• Idarucizumab reverses dabigatran

• But need to treat cause of bleeding also

− 2.5 - 11 hours to stop bleeding after antibody

administered

• Allowed emergency surgery

• Should be used for ICH or urgent surgery


Our Protocol

1. Indication: ICH for patient on dabigatran

2. Baseline thrombin time and aPTT

− Not to screen for use but to assess drug use

3. Five grams administered as 2.5 gram bolus one

right after other

4. Consider for emergency surgery if TT/aPTT

elevated


Xa Blockers

• Prothrombin Complex concentrates

– Animal and human studies

• No difference in bleeding outcomes in warfarin vs DOAC

ICH patients


Coagulation factor Xa (recombinant), inactivated-

zhzo

• “Andexxa”

• Recombinant fXa derivative

▪ Catalytically inactive

▪ Lacks the Gla-domain

− Bolus then 2 hour infusion

• Reverses both direct and indirect Xa inhibitors

• Approved May 2018 but available in limited quantities.


Coagulation factor Xa, inactivated-zhzo

28

• Will reverse rivaroxaban and apixaban

• Will likely work for other “bans” as well but not FDA

approved

• Should theoretically work to reverse Fondaparinux,

but is no trial data yet.

Package insert contains a black box warning if patient

has had recent thromboembolic events.

Very expensive, use only for life threatening bleeding.


What if you don’t have the fancy new drugs

• Prothrombin Complex Concentrates

(4 factor)

• Increasing data on effectiveness

• Dose - 50 units/kg


Case 4

30

• A 47 year old man with alcoholic cirrhosis presents

with hematemesis.

• Hgb = 8.0/gldL

• PT/INR = 1.9

• aPTT= 42 seconds

• Platelet count= 50K/µL


Liver Disease

• Multiple defects in coagulation

❖Decreased synthesis of factors

❖Decreased platelets

❖Decreased platelet function

• But clinical data also shows increase in

thrombosis

❖Risk of thrombosis increased three-fold


Incidence of venous thromboembolism based

on Child-Pugh Stage.

Dabbagh O et al. Chest 2010;137:1145-114932© 2018 College of American Pathologists. Materials are used with the permission of the faculty.

Hemostasis in Liver Disease

• Levels of natural anticoagulants and inhibitors of

coagulation also reduced

− Antithrombin

− Protein C

− Protein S

• Coagulation is “rebalanced”

− Thrombin generation is normal


34

Hepatology 44:440-445, 2006


Transfusions in Upper GI Bleeding

• Large Spanish study of UGI

• N = 921

− Ulcers 49%

− Varices 21%

• RCT

− Restrictive: Hgb = 7 (7-9)

− Liberal: Hbg = 9 (9-11)

35

NEJM 368:11-21, 2013


Results

36

Result Restrictive Liberal p

Death 23 (5%) 41 (9%) 0.02

Death –bleeding 3 (0.7%) 14

(3.1%)

0.01

Further bleeding 45 (10%) 71 (16) 0.01

No transfusion 225 (51%) 61 (14%) <

0.001

Transfusion reaction 14 (3%) 38 (9%) 0.001

Cardiac

complication

49 (11%) 70 (16%) 0.04


Case 4

37

5 months later, the patient is admitted with ascites and

hepatic encephalopathy. There is no evidence of

bleeding. INR = 7.0 and platelet count is 60K/µL.


The INR

• Only standardized for stable patients on warfarin

• Unreliable in liver disease

− VII falls more than II and XI

− Also if fibrinogen is low will falsely raise INR

• Not a predictor of bleeding


TEG in Liver Disease

• Normal R

• High normal α angle

• High normal MA

• Normal LY30

• Overall – Normal

• INR 2.21

• Platelets – 128,000


Case 5

• 73 year old man presents with a ruptured abdominal aortic

aneurysm.

• The patient is Rh(D) negative with a negative antibody

screen.


Rh(D): Basic points

41

A. Unlike ABO antibodies, Rh(D) negative

individuals do not have naturally occurring

anti-D.

B. Even if the patient has anti-D, intravascular

hemolysis is unlikely to occur.

C. Group O Rh(D) negative blood constitutes

only 7-9% of the community supply.


Frequency in Caucasian Population

O + 36% O- 9%

A+ 34% A- 8%

B+ 8% B- 2%

AB+ 2.5% AB- 0.5%


Extravascular

hemolysis

Much less symptomatic than

intravascular hemolysis. Decreased

hematocrit may be the main finding.


Laboratory results are not yet available

1. Is it appropriate to transfuse at a 1:1:1 ratio?

2. What does that even mean?

3. If a 1:1:1 protocol is started, for how long

should it continue?


What does a 1:1:1 ratio even mean?

Definition:

• 1 whole blood derived platelet: 1 plasma: 1

RBC

• In most systems: 1 platelet dose: 6 plasma: 6

RBC


Not long. Risks:

• Respiratory compromise

• Abdominal compartment syndrome

• Suboptimal management of the coagulopathy

• eg, heparin, hemophilia, DIC

If one starts a 1:1:1 protocol, for how long should it

continue?


Does a 1:1:1 ratio apply in a non-trauma

patient?

• Probably not, unless the patient has shock,

acidosis, and significant tissue injury.

• However, some replacement of coagulation

factors and (eventually) platelets is warranted.


Brief history of 1:1:1 idea

• Idea first suggested in field of combat.

• Civilian trauma centers started to look at their

practice.

– This generated much retrospective data with

many variables, making a meta-analysis

difficult.

• PROMMTT trial

• PROPPR trial


Prospective, Observational, Multicenter,

Major Trauma Transfusion Study

• 10 US level 1 trauma centers

• 1245 patients

• Received at least 1 RBC within 6 hrs of

admission

• Received at least 3 blood products within

24hrs


PROMMTT Objective

To relate in-hospital mortality to:

- early transfusion of plasma and/or platelets

- Time-varying plasma:RBC and platelet:RBC

ratios.


PROMMTT Results

• Increased ratios of plasma:RBC and

platelet:RBCs were independently

associated with decreased 6 hr

mortality, when hemorrhagic death

predominated.

• In the first 6 hrs, patients with ratios

less than 1:2 were 3-4 times more likely

to die compared to 1:1.


From: The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study: Comparative

Effectiveness of a Time-Varying Treatment With Competing Risks

JAMA Surg. 2013;148(2):127-136. doi:10.1001/2013.jamasurg.387

Figure 1. Blood product use in the first 6 hours in 2 Prospective, Observational, Multicenter, Major Trauma Transfusion Study patients. Patient 1 (A) had an

Injury Severity Score of 48 and died of hemorrhage at 1 hour 7 minutes after emergency department admission. Patient 2 (B) had an Injury Severity Score of 57

and was discharged to another acute care hospital at 27 days. Note the constantly changing ratios over time. For example, patient 1 received cumulative

plasma:platelet:red blood cell (RBC) ratios of 0:0:1, 0:0:3, 0:0:6, 4:6:6, and 5:6:6 at 15, 30, 45, 60, and 75 minutes, respectively, while patient 2 received

cumulative plasma:platelet:RBC ratios of 0:0:1, 0:0:4, 0:0:4, 2:0:6, and 2:0:10 at those same times.

Figure Legend:


From: The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study: Comparative

Effectiveness of a Time-Varying Treatment With Competing Risks

JAMA Surg. 2013;148(2):127-136. doi:10.1001/2013.jamasurg.387

Figure 2. The bars represent cumulative ratios at the start of each time interval. Most patients received a plasma:red blood cell

(RBC) ratio of 1:2 or higher by 3 hours (A) and a platelet:RBC ratio of 1:2 or higher by 6 hours (B). In the last time interval (24

hours), the percentage of patients receiving 0 units of platelets or plasma increases, reflecting the dynamic cohort with newly

eligible patients entering and others exiting owing to death in the previous interval.

Figure Legend:


Holcomb JB et al. JAMA 2015; 313(5):471-482.


PROPPR Trial

• RCT involving 680 patients with severe trauma.

• 1:1:1 vs 1:1:2 ratio. Blood products were

administered in a pre-specified order to maintain

assigned ratios.

• Primary outcomes: 24 hr and 30 day mortality.

• Secondary outcomes: time to hemostasis, ICU

free days, functional status at discharge.


Survival 1:1 vs 1:2

57

Holcomb et al JAMA 2015;313:471 – 482.

Less exsanguination at 24 hours with 1:1

NO increase in complications with 1:1


PROPPR Trial- results

• No significant difference in primary or

secondary outcome >> no significant

difference in mortality with either strategy.

• But a post-hoc analysis indicated that death

by exsanguination was significantly

decreased in the intervention group.


Are guidelines appropriate for severe trauma

patients applicable to non-trauma patients?

2011 Consensus conference indicates

no, unless the patient has shock,

acidosis, and significant tissue injury.

.

59

Dzik et al. Critical Care 2011;15:242


Literature is emerging about MTP use in

non-trauma patients

• Retrospective, with relatively small numbers.

• Patients are typically older and sicker at baseline than

trauma patients.

• Similar to initial retrospective trauma literature, significant

variability exists.


Association Between Ratio of FFP to RBC

during Massive Transfusion and Survival

Among Patients Without Traumatic Injury

62

• Retrospective review of all massive transfusions

at Massachusetts General Hospital from 2009-

2012.

• Main measure was the examination of FFP:RBC

transfusion ratios for patients without trauma.


Findings

63

Almost 90% of massive transfusions took place in

patients without trauma:

• Higher numbers of cardiac and liver transplant

surgery, with trauma 3rd highest patient

population.

Overall, there was no difference in 30 day mortality

between the high FFP:RBC ratio and the low FFP:RBC

ratio.


Findings, cont’d

64

However, significant differences in 30 day mortality

rates were observed within individual services.

For vascular surgery, a high ratio was associated with

decreased mortality (p = .045).

But for general surgery, orthopedic surgery, and

medicine, a high ratio was associated with increased

mortality.


Massive transfusion in patients without trauma


For rAAA patients, there are other rare

retrospective studies indicating that increased

plasma: RBC ratio improves outcome.

Mell et al Surgery 2010;148:955-62.


Coagulopathy in rAAA patients

• Most do not start out with a coagulation

disorder unless on anti-platelet therapy,etc.

• Dilutional coagulopathy can develop if only

RBCs administered.

• A rare patient will have/develop DIC.


Consensus committee recommendations

1. For patients with critical bleeding, immediate

application of a ‘foundation ratio’ of blood components.

Example, 6 RBCs and 3 FFP for the initial treatment.

2. Adjustments to the foundation ratio based on the

clinical course and results of laboratory tests using goal

directed therapy.


Better patient outcomes with massive transfusion

may be more due to:

• Improved communication.

• Decreased time of delivery of blood products.

• Clearly defined roles, responsibilities, and resource

allocation.


Thromboelastrography

• Point of care test using fresh whole blood.

• Measures tensile strength of forming clot.


Thromboelastrography, cont’d


Thromboelastrography, cont’d

• Drawbacks

− Lack of familiarity

• TEG based protocols

− Need to run sample in 4 minutes

− Who runs samples and QA machines?


Patient with Liver Disease

• Normal R

• High normal α angle

• High normal MA

• Normal LY30

• Overall – Normal

• INR 2.21

• Platelets – 128,000


TEG Based Transfusion Protocol

TEG Parameter Interpretation Action

R Time Time to fibrin formation Increased - FFP

K time Kinetics (2-20mm ) Increased - Cryo

Alpha Angle r/k slope of tracing Decreased - Cryo

Maximal

Amplitude

Strength and stability of

thrombusDecreased - plts

Whole blood

Lysis IndexFibrinolysis

Increased -

antifibrinolytic


76

Sounds good, but…

Many of the values actually reflect a mixture of things.

For example:

- the angle represents a combination of coagulation

factors, platelets, and fibrinogen.

- the R value represents a combination of coagulation

factors and platelets.

Thombin is the platelet activator in TEG. It is a very

powerful activator, so TEG will miss platelet dysfunction.


78

Studies done often compare TEG or ROTEM to

traditional lab testing that takes 45-60 minutes. What

is needed is a comparison of TEG or ROTEM to

traditional testing that takes 20 minutes.

If we cannot achieve a 20 minute turn around time,

TEG will be used because it is available within the

“golden hour.”


Goal: Reasonably accurate coagulation tests within 20

minutes for an actively bleeding patient.

• Stopped performing checks for clotting or hemolysis

>> >> 9% exceeded the 20 minute goal.

• Revised the fibrinogen assay with an expanded

calibration range.

>> 2% exceeded the 20 minute goal


Hypothermia

AcidosisCoagulopathy

The Lethal Triad

What can we take away from the trauma

literature?


Other Ideas we can take away:

Laboratory value turn around time must be

more rapid than traditional testing, and often

requires a special signal, such as activation of a

hemorrhage protocol.


And possibly:

Improved predictors for who will require

massive transfusion:

• Trauma patients requiring >3 units PRBCs

per hour.

• Shock index: ratio of heart rate to systolic

blood pressure.


In Summary

For patients with significant blood loss, early

plasma infusion is likely to improve outcome.

During cases of ongoing blood loss,

component therapy based on rapid laboratory

values should be pursued as soon as

possible.


Case 6

84

A 30 year old Rh(D) negative woman delivers

a baby. Upon delivery of the placenta, the

patient experiences blood loss estimated at

1700mL. The clinical team begins their

hemorrhage protocol.


Remember

85

By convention:

Screening cell I is always Rh(D) positive (R1R1 = DCe/DCe)

Screening cell II is always Rh(D) positive (R2R2 = DcE/DcE)

Screening cell III is always Rh(D) negative (rr = ce/ce)

Good prenatal care will result in cells I and II

showing agglutination due to Rh immune

globulin administration at 28 weeks gestation.


Post Partum Hemorrhage (PPH)

• Rare: > 10 units of blood 6/100,000 deliveries

• Deadly: 3-11% of maternal deaths

• Incidence is increasing

• Can be truly massive “audible” bleeding


PPH - Plasma: RBC 1:1 Ratio• Recent data suggesting that a fix ratio of 1:1 RBC:FFP associated

with better outcomes in trauma

• Deemphasizes on laboratory testing for initiation hemostatic

resuscitation

• Logic extending to non-trauma massive transfusions such as PPH

but limited data

• Why early plasma?

− Takes time to run coagulation tests

− Many patients with coagulopathies at time of hemorrhage

• Placenta previa, abruptions, amniotic fluid embolism…

− Plasma may contain beneficial factors that help in massive

bleeding87© 2018 College of American Pathologists. Materials are used with the permission of the faculty.

Recommendations

• Start with 4 RBCs

• Transfuse 4 units plasma

• Transfuse 4 more RBCs

• 4 more units of plasma

• 2 cryopools and 1 dose platelets

J Thromb Haemost. 2016 Jan;14(1):205-10


Why Early Plasma?

• Takes time to run coagulation tests

• Many patients with coagulopathies at time of hemorrhage

• Plasma may contain beneficial factors that help in massive

bleeding


65%

34%

20%

0

10

20

30

40

50

60

70

0:22 - 1:4 1:3.9 - 1:2.1 1:2 - 1:0.59

Mo

rtali

ty %

Chi Square

RB: p=0.006

RG: p<0.001

BG: p=0.034

Effect of FFP:RBC Ratio on Overall Mortality

n=31 n=56 n=165

FFP:RBC RatioBorgman et al. J Trauma. 2007;63:805-813.


However… in PPH

• Thrombocytopenia less common

− Unless severe bleeding or DIC


Fibrinogen; the Forgotten Factor

• Crucial for forming hemostatic plug

• Crucial for INR and PTT testing

• Levels rise in normal pregnancy

• Lower levels predictors of post-partum hemorrhage

• Newer data indicate higher targets in obstetrical

bleeding

− > 200 mg/dl


Fibrin

LysLys LysLys LysLys Lys Lys

Plasmin


LysLys LysLys LysLysLys Lys

Fibrin

Lysine EACA TXA


Fig 2 Cumulative meta-analysis of the effect of tranexamic acid in surgery on

risk of blood transfusion in adequately concealed trials.

Katharine Ker et al. BMJ 2012;344:bmj.e3054©2012 by British Medical Journal

Publishing Group


TXA reduces bleeding in surgery

TX

A

TXA better TXA worse

0.61 (0.57-

0.66)

RR (95% CI)

0.4 0.8 1.2 1.6

Transfusion

TX

A

RR (95% CI)

TXA better TXA worse

0 0.4 0.8 1.2 1.6

0.57 (0.34-

0.98)

Mortality

65 trials (4,842 patients) 30 trials (2,917

patients)


TXA

• Small trials showed reduced blood loss in PPH

• WOMEN Trial

– Blood loss > 500 mL after vaginal birth or 1000 mL

after C-section or any blood loss

– sufficient to compromise hemodynamic stability.

– Intervention: one gram of TXA

– Patients: TXA: 10,036 Placebo: 9,985

Lancet 2017:389:2105-16


TXA: WOMEN TRIAL: RESULTS

• Death due to PPH

− TXA 1.5% (155/10,036) vs Placebo 1.9% (191/9,985)

− RR: 0.81 (CI 0.65 – 1.00, p = 0.045)

− Absolute risk reduction = 0.4%

− No increased in thrombosis

• TXA should be used if significant PPH present. A second

dose can be given if needed. Administer within 3 hours

of the onset of PPH.


TXA: WOMEN TRIAL: CONCLUSIONS

• TXA should be used if significant PPH present.

• A second dose can be given if needed.

• Administer within 3 hours of the onset of PPH.


Prohemostastic Drug: rVIIa

• Decreasing use in massive transfusions with negative trial

data and increase risk of thrombosis

• Open label study in PHH showed 60 ug/kg reduced need

for procedure but not blood loss or blood product usage

• If bleeding is ongoing and labs are normal consider 60-90

ug/kg

• Remember

– Need fibrinogen > 200mg/dl

– Need pH > 7.2 102© 2018 College of American Pathologists. Materials are used with the permission of the faculty.

Prohemostastic Drugs: PCC

• Increasing use of PCC in massive bleeding in order

to give coagulation factors with decrease volume

• Increasing use in trauma: 50 units/kg if

coagulopathy persist despite ongoing hemostatic

resuscitation

− RCT ongoing

• Thrombosis is a concern

• Not recommend for PPH until there is more data


PPH: Massive Transfusion Protocols

• Key to get the right blood products fast to the right place

• Need to know

− Who can initiate (providers, transfusion service)

− Sending out the right products

• Box of blood

• “Trauma 4x4”

− Keeping track of products and labs

• Practice runs for less busy hospitals

• MTP associated with better outcomes


Case 7

106

A 39 year old man requires a renal biopsy. The patient

is oliguric and rapidly progressive

glomerulonephritis is suspected. Platelets are

requested.

Current platelet count = 57K

PT/INR and aPTT are within normal limits.

Serum creatinine = 5.0 mg/dL

Blood urea nitrogen = 100mg/dL


Uremia and Platelets

• Milieu of uremia inhibitors platelet function

• Transfused platelets rapidly inhibited

• Recommendations

− Dialysis to lower “toxin” level

− DDAVP improved platelet function

− Cryoprecipitate often recommend but unreliable


AABB Platelet Guidelines

• Recommendation 1: The AABB recommends transfusing

hospitalized adult patients who have therapy-induced hypoproliferative thrombocytopenia with a platelet count of 10 ×109 cells/L or less to reduce the risk for spontaneous bleeding.

• Recommendation 2: The AABB suggests prophylactic platelet

transfusion for patients having elective central venous catheter placement with a platelet count less than 20 ×109 cells/L.


transfusion for patients having elective diagnostic lumbar

puncture with a platelet count less than 50 ×109 cells/L.


AABB Platelet Guidelines, cont’d


transfusion for patients having major elective nonneuraxialsurgery with a platelet count less than 50 ×109 cells/L.

• Recommendation 5: The AABB recommends against routine

prophylactic platelet transfusion for patients who are

nonthrombocytopenic and have cardiac surgery with

cardiopulmonary bypass (CPB).

• Recommendation 6: The AABB cannot recommend for or

against platelet transfusion for patients receiving antiplatelet

therapy who have intracranial hemorrhage (traumatic or

spontaneous).


- Helps to show the strength of the evidence

behind the recommendations.

111

Kumar et al. Platelet

transfusion: a systematic

review of the clinical

evidence. Transfusion 2015;55:

1116-1127.


PATCH Trial-

112

Platelet transfusion Versus Standard Care After Acute Stroke due to

Spontaneous Cerebral Haemorrhage Associated with Antiplatelet

Therapy Lancet 2016.

• Multicenter, open-label, masked endpoint, Randomized trial.

• 60 hospitals in Netherlands, UK, and France

• Enrolled adult patients with non-traumatic ICH on anti-platelet

therapy. Glasgow Coma Scale of at least 8-15. Platelet

transfusion available within 6 hours of onset of symptoms.

• Randomized to standard care or standard care with platelet

transfusion within 90 minutes of allocation.


Patients

113

Platelets Control

Age 74.2 73.5

Men % 55 57

Aspirin 73 84

Asprin/dipyridamole 19 14

ADP inhibitors 4 1

ICH volume 13.1 8.0

ICH score 1 1

GCS 5-12 19 12


PATCH- Outcome measures

• Primary: Shift toward death or difference in functional

outcome at 3 months after randomization rated on a modified

Rankin Scale (mRS).

• Secondary:

− Survival at 3 months

− Poor outcome defined as mRS 4-6

− Growth in hemorrhage after 24 hrs

− Serious adverse events such as complications of the

hemorrhage


PATCH- Results

115

posted in Clinical Neurology

by Salim Rezaie


PATCH conclusions

116

Platelet transfusion increases the risk of death or

dependence in patients with an acute intracerebral

hemorrhage while taking antiplatelet therapy.

Avoid making this part of standard care.

Baharoglu MI et al. Lancet 2016 June 25;387 (10038): 2605-13.


The evidence for adequate platelet count and

neuraxial anesthesia in pregnancy exists in

small studies; no RCT available. Standard of

care is often 80K despite this lack of data.

No RCT exist for platelet count and central

venous catheter placement. One relatively

small trial is being done in patients with

chronic liver disease. Risk appears to be low if

an ultrasound-guided technique is used.

Stanworth, SJ. Cochrane database of Systematic Reviews 2015 and 2016.


Summary

118

TM Consultation:

1. Evaluate available data prior to calling clinical

team. History, drugs, coagulation results,

products given so far.

2. Determine causes for bleeding and the most

appropriate treatment.


Pearls

119

1. Subcutaneous vitamin K is not effective.

2. KCentra is FDA approved to reverse warfarin

effect in the face of life-threatening bleeding.

3. 3-factor PCCs still require plasma for the factor VII.

4. Know which type of crossmatch is being done and

whether the clinical situation calls for something

faster.


Pearls, cont’d

120

5. ESLD patients have relatively normal thrombin

generation, despite the abnormal PT/INR.

6. The indications for plasma infusion are few; the

indication for prophylactic infusion are non-

existent.

7. Plasma is needed early to prevent irreversible

coagulopathy in the setting of massive transfusion.


Pearls, cont’d

121

8. Fibrinogen less than 200mg/dL is a predictor of

severe post-partum hemorrhage.

9. TXA should be used early in post-partum

hemorrhage.

10. Cryoprecipitate is much more effective at

increasing serum fibrinogen level quickly,

compared to plasma.

11. Infusing new platelets into a uremic environment is

ineffective.


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