Coagulation Disorders in Pregnancy :

Obstetrician’s nightmare
Dr Girija Wagh

Day & Date: Friday , 2nd September, 2018 Dr Meenu Agarwal

Time of session: 03.30 pm to 04.30 pm - Panel Discussion :
Coagulation Disorders in Pregnancy : Obstetrician’s
nightmare
Allotted time: 60 minutes
 the panelists
Amit Basu

Amina Prasad

Kavita Babbar

Santosh Jaybhaye

Sudhir Adhikari

Rubina Sohail

Abhijeet Deshpande

AICOG 2018 ORISSA 2

Basics

Assessment

Management principles

Case scenarios
 ▪The mechanisms of hemostasis are complex.

▪The process of clot formation occurs on multiple levels with

intricate feedback systems that are not well represented in
the typical coagulation cascade.

▪This process is even more complex in the parturient, where

changes such as physiological anaemia and fluctuating
coagulation factor concentrations alter the balance between
bleeding and clot formation in preparation for peripartum
blood loss.

De Lange NM, Lancé MD, de Groot R, Beckers EAM,Henskens YM, Scheepers HCJ. Obstetric hemorrhage and coagulation:an update. Thromboelastography,
thromboelastometry,and conventional coagulation tests in the diagnosis and prediction of postpartum hemorrhage.Obstet Gynecol Surv 2012; 67: 426–35

Collis RE, Collins PW. Haemostatic management of obstetric haemorrhage. Anaesthesia 2015; 70 (Suppl. 1): 78–e28
 systemic activation of blood coagulation

Disseminated
intravascular
coagulation (DIC) is a
pathologic disruption of
the finely balanced
process of hemostasis.
generation and deposition of fibrin and formation of
microvascular thrombi in the small blood vessels throughout
the body

multiple organ dysfunction

5
 DIC CASCADE
Clot formation
6
 pathophysiologic processes

NET: neutrophil extracellular trap

PT: prothrombin time
aPTT: activated partial thromboplastin time
FDPs: fibrin degradation products;
dsDNA: double-stranded DNA
MAHA: microangiopathic hemolytic anemia.
laboratory abnormalities

7
PREGNANCY IS SPECIAL !?
Preeclampsia, eclampsia, (HELLP) syndrome : endothelial cell damage.

Acute fatty liver : impaired hepatic production of coagulation factors

impaired clearance of fibrin degradation products.
Shock : reduced tissue perfusion
reduced natural clearance of anticoagulants
Hemorrhage : severe tissue hypoxia : release of tissue factor on/from
damaged cells
Infection or inflammation : an interaction between DIC and systemic
inflammatory response syndrome (SIRS)

8
HOW MUCH ???
INCIDENCE ??

9
Prevalence of DIC in Pregnancy

Ranges from 0.03 to 0.35 % or 12.5 per 10,000 delivery Hospitalizations

1 to 5 percent of all cases of DIC in high-resource countries; the

proportion of DIC cases attributable to pregnancy complications is
higher in low-resource countries

frequency of DIC in women with specific pregnancy complications can

be quite high

10
 What are these
special conditions
during pregnancy ?

11
Antecedent conditions causing DIC / %
Placental Abruption 37% concealed retroplacental clot

Postpartum hemorrhage 29% tissue trauma or retained products of conception

Preeclampsia/eclampsia/ 14% Endothelial dysfunction

HELLP
Acute fatty liver of 8% impaired hepatic synthesis of coagulation factors
pregnancy
Amniotic fluid embolism 6% Amniotic fluid is rich in procoagulants and anticoagulants

Pregnancy-related sepsis 6% retention of a dead fetus over several weeks is a rare cause
(eg, septic abortion) of DIC
 IS THIS PPH? CAUSE ??
• Risk factors ? • Assess the fundus
• Blood loss ? • Inspect the LGT
• Explore the uterus
TONE o Retained placental
4 TISSUE
TRAUMA
fragments
o Uterine rupture
THROMBUS
o Uterine inversion
• Assess coagulation
girijawagh@gmail.com 9422000584 • ` 18/01/2018 14
What clinical evaluation will put you
on a suspicion of DIC
 SIGNS ::: BE ALERT
• Severe uterine bleeding and/or diffuse oozing of blood from skin
(eg, at intravenous sites) or mucosa (eg, from a bladder catheter)
• Hepatic rupture and intra-abdominal bleeding.
• Substantial uterine bleeding may not be appreciated initially if
most of the blood is retained in utero behind the placenta (eg,
"concealed abruption").
• Signs of shock (eg, tachycardia, hypotension, weak peripheral
pulses, altered mental status, cool extremities, narrow pulse
pressure [<25 mmHg])
• Organ dysfunction may be present (eg, acute renal failure, hepatic
dysfunction, acute lung injury, neurologic dysfunction)
 Any laboratory findings ?
There is no single laboratory test that
is sensitive and specific for DIC
 Laboratory testing includes the following:
Complete blood count (CBC) with platelet count and differential.
●

●Coagulation studies including prothrombin time (PT), activated partial

thromboplastin time (aPTT), fibrinogen level, and D-dimer.

●Blood urea nitrogen (BUN) and creatinine.

●Liver function tests.

●Blood and urine cultures in patients with suspected sepsis.

In cases where intrauterine infection is suspected, amniotic fluid culture

Any bedside test ?
Crude but swift
Determine the clotting time of 5 ml of blood
 DIFFERENTIAL DIAGNOSIS ?
 DIC in pregnancy includes other causes of bleeding, thrombosis, and/or
organ damage.
 These conditions may coexist with DIC
 Contribute to the pathogenesis of DIC
• Postpartum hemorrhage with dilutional coagulopathy
• Primary thrombotic microangiopathy : TTP
• Von Willebrand disease :
• Antiphospholipid syndrome
• Pulmonary embolism
• Heparin-induced thrombocytopenia
• Transfusion reaction
Assess fetal status : ??
Considerations ?
 Situational individualised
• Salvagibility
• IUD : CONNOTATIONS ?
• JEOPARDY ?
• TEMPORISATION ?
MATERNAL MANAGEMENT
OVERVIEW ?
• Resuscitation aims to achieve euvolemia
• Normalize tissue oxygen delivery
• Resolve acidosis and coagulopathy
– appropriate fluid therapy and transfusion (using near-
equal amounts of packed red blood cells [RBCs],
plasma, and platelets)
– warming the patient
– appropriate airway and ventilatory management.
HOW TO ASSESS BLOOD LOSS ?
NEAR ACCURATE ?
Blood loss is evaluated indirectly by assessment of vital
signs: become overt late in pregnancy
• In NON ANESTHETISED WOMEN ……………..
• ●Systolic blood pressure <100 mmHg
15 -25 %
• ●Pulse >100 bpm BV

• ●Urine output <30 mL/hour

• Other signs and symptoms of hemodynamic : altered level of

consciousness; shortness of breath; cold, clammy skin; and pallor.
New approach to
transfusion ??
 Transfusion Protocols for PPH
• The WHO recommends that health facilities have a formal protocol in place
for PPH management.
• Recent resuscitation algorithms of PPH are modeled after trauma, and
massive transfusion protocols demonstrate improved patient outcomes.
• Focus on the creation of a multidisciplinary team for patient care, initiation
of appropriate laboratory studies, restoration of fluid volume, correction of
a coagulopathy with blood components and factors, appropriate responses
to laboratory and hemodynamic assessments and correction of the primary
cause of bleeding
Conventional resuscitation follows a stepwise approach

• Starting with intravenous fluids, followed by red blood cells

(RBCs) and clotting factors or platelets.
• While this approach corrects hypovolemia, it worsens
existing
– Dilutional Coagulopathy
– Enhances Fibrinolysis
– Contributes To Acidemia
– Hypothermia.
• Recent advances from trauma medicine suggest that
increasing the ratio of fresh frozen plasma (FFP) to RBCs
from 1:3 and 1:4 to 1:1 or 1:2 improves survival.
 COAGULOPATHY
• The fibrinogen decrease seen an early predictor of hemorrhage
severity.
• Treatment of hypofibrinogenemia involves cryoprecipitate
transfusion to maintain fibrinogen levels (100–200 mg/dl).
• Fibrinogen concentrate may be an advantageous alternative.
– Fibrinogen concentrate is stable at room temperature and can be rapidly administered, unlike
cryoprecipitate, which must be kept frozen and then thawed prior to administration.
– Fibrinogen concentrate also contains a greater concentration of fibrinogen and more reliably
increases fibrinogen levels.
• Widespread belief in benefits of early fibrinogen substitution for
PPH spurred this off-label usage; the first RCT (FIB-PPH) is currently
in progress.
Thromboelastography (TEG) or
ROTEM (thromboelastometry) ?
What are these ?
 Thromboelastograph
• Rapid blood product selection may benefit from the use of
a, a point-of-care device that examines clot formation and
dissolution in whole blood, and provides faster results than
laboratory testing.
• An observational study of thromboelastograph
measurements found that clot amplitude and maximum
clot firmness were strongly correlated with fibrinogen
levels.
• Availability of the thromboelastograph in the labor ward
could be an important tool for managing PPH.
Call for help & notify

IV Access

Fluids and bloods

Oxygen saturation

Warm

Labs

Fetal assessment

Maternal assessment

Facility checklists
 Rational reckoner for Massive
Obstetric hemorrhage :
• Massive Obstetric hemorrhage blood and blood component
management should be looked at as 4 different problems
– loss of volume
– loss of coagulation factors
– platelet deficits
– loss of red cells (hypoxia).
• They should be corrected with the help of red cells, and
replacement of clotting factors with fresh frozen plasma,
cryoprecipitate and platelet concentrate and volume
expander.
 Practical Tips
• If there is obstetric hemorrhage with DIC most of our patients need
– 4 platelets
– 4 cryoprecipitate
– 4 FFPs
– 4 red cells.
• At the first sign of possible obstetric DIC we asked our blood bank
and resident staff to be ready with this kind of transfusion support.
• We call it rule of 4.
TRANSFUSION TARGETS ??
SHOULD THERE BE ANY ?
TARGET TRANSFUSION
• Hemoglobin ≥7 g/dL

• Platelet count ≥50,000/microL

• Fibrinogen ≥300 mg/dL

• Prothrombin time (PT) and

activated partial
thromboplastin time (aPTT)
less than 1.5 times control
MTP : Massive transfusion protocol ?
Rule of 4 for massive blood transfusion in obstetric hemorrhage
fresh frozen plasma (FFP), platelets, and packed red blood cells (PRBCs) in a 1:1:1 ratio.

 4 platelets, 4 Cryoprecipitate ,4 FFPs and 4 PCVs or RCC

 One IV access for PCVs and /or RCC and to be given till the hemoglobin is 9g/dl and is maintained.
 FFPs,CPs and plateltes to be transfused form the other access

Important points : Ratio of FFP to PCVs of 1: 1 or 1:2 is known to improve survival

 Transfusion goals :
Hemoglobin : 8-9 g/dl ; maintained
Platelets more than 75000/ mL
PT and PTT less than 1.5 times the control
FFP : Fresh frozen plasma ;PCV : Packed cell volume ; RCC :Red Cell Concentrate;CP : Cryoprecipitate ,PT
: Prothrombin time;PTT : activated prothrombin time
 Hemostatic agents
• Recombinant activated
• Tranexamic acid factor VII(rFVIIa)
– Prevents binding of plasminogen – Enhancement of rate of
to plasmin and fibrin thrombin generation : fully
– Intractable PPH : coagulation stabilized fibrin plug resistant
– Only one paper: placenta acreta : to lysis
1G IVproves
If bleeding 4 hrly:: 3G – 60-120μg/kg
unresponsive to uterotonics, consideration
IV may be
given to tranexamic acid (TXA), a synthetic derivative of lysine with
antifibrinolytic properties, or recombinant activated factor VII (rvFIIa

18/01/2018 girijawagh@gmail.com 9422000584 45

 EVIDENCE ??
• A 2010 Cochrane Review of TXA reported decreased blood loss
after vaginal and cesarean birth but called for further investigation
around efficacy and safety.
• Two more recent randomized controlled trials (RCT) concurred, yet
were underpowered to evaluate safety concerns such as
thrombolytic events.
• The WOMAN Trial is currently evaluating TXA for PPH treatment.
• WHO provides a weak recommendation for TXA where oxytocin
and prostaglandins fail to control atonic PPH
• RCOG reports that fibrinolytic inhibitors seldom have a place in PPH
management.[
47
 Before
admission

USG : 38W 6DAY 19/08 /17

▪Twin live IU fetuses DADC
▪Fetus1 : 35-36 weeks : breech
▪Fetus 2 : 34 weeks : transverse : mild asymmetrical
IUGR
▪Oligohydramnios
▪Placenta 1 : FA :::: 2 : FP

48
 On Admission : 20/08
▪Loading dose of MgSO4 : given ▪Abdomen scan : L/S/K/P : N
▪Zuspan regimen started ▪Minimal ascites ,pleural
▪Labs send effusion
▪PCVs 2/4FFP/4CP booked ▪ OBG scan : WNL : Consistent
▪Labetolol continued with twin gestation
▪Close monitoring in HDU
▪High risk information
49
Reports came in
 Hb TLC PLT Urine SAP SGOT SGPT Bil BUN Cre LDH
g/dl Iu/L

16/08 11.8 10950 1.79 3+ 418 42 42 0.67 44 Na 890

20/08 5.4 10900 80000 3+ 420 195 155 0.6 43 0.89 1990

Fragmented RBCs Coagulogram Before CS After CS

PT sec 9.0 12.2

PT control 10.6
Lab range 9.6-13.4
Mean N PT 11.6
INR 0.78 1.05
Plasma fibrinogen 652 353

APTT 26.5 27.9

Control 27.5
51 APTT range 26.6-35.5
 Diagnosis ?
Severe PRECLAMPSIA at term
Late onset preclampsia
HELLP

52
 HELLP alerts
• Any vomiting during pregnancy in the
second half : high index of suspicion

• Patient can rapidly deteriorate after

initial symptoms

• Early diagnosis gives the best chance

 HELLP
• HELLP stands for: Hemolysis (abnormal smear), Elevated liver enzymes (
serum SGOT >70 U/L serum LDH >600 U/L , and Low Platelets(< 100000)

• OCCURRENCE- 20% of preeclampsia patients.

• CAUSE-
– endothelial and microvascular injury
– increased vascular tone
– platelet aggregation.

•
 Fragmented RBCs seen : 8PCVs + 6FFPS +4 RDP
Coagulation profile : deranged
Se electrolytes : Se Potassium : 6.1mEq/L : correction
done ( GI drip )
ECG : WNL
CS deferred till correction of hyperkalemia .

CS done under GA after electrolyte imbalance

was corrected
No PPH
Intubated for : 24 hours
MgSO4 continued for 24 hours

55
 Hb TLC PLT Urine SAP SGOT SGPT Bil BUN Cre LDH
g/dl Iu/L

16/08 11.8 10950 1.79 Wnl 418 42 42 0.67 44 Na 890

20/08 5.4 10900 80000 P+1 195 155 0.6 0.89 1990

23/08 9.0 19800 78000 +1 542 655 1105 0.64

56
 Hematologic Evaluation
▪ CBC count
▪Incidental platelet count < 150,000/µL
▫75% are secondary to dilutional thrombocytopenia of pregnancy,
▪24% are due to preeclampsia,
▪about 1% : other platelet disorders not related to pregnancy.
Counts < 100,000/µL
▪ Preeclampsia
▪ Immune thrombocytopenic purpura (ITP).

57
 PBS: Peripheral blood smear

Examination of the peripheral blood smear for evidence of

microangiopathic hemolysis and thrombocytopenia may
reveal the presence of red blood cell (RBC) fragments.
the diagnoses of hemolytic-uremic syndrome
(HUS), thrombotic thrombocytopenic purpura (TTP), and
HELLP syndrome (hemolysis, elevated liver enzymes, and
low platelet [count]) should also be considered.

58
 CBC : careful interpretation necessary
▪Hemoglobin levels > 13 g/dL suggest the presence of
hemoconcentration.
▪Low levels may be due to microangiopathic hemolysis or iron
deficiency.

▪Prothrombin time (PT) and/or international normalized ratio

(INR) and/or activated partial prothrombin time (aPTT) results
may be abnormal in consumptive coagulopathy
and disseminated intravascular coagulopathy (DIC) complicating
severe preeclampsia.

▪However, checking the PT/INR/aPTT is not necessary in the

absence of abnormal liver transaminases or thrombocytopenia .

59
 Post op
▪BP : 180/110 ▪29/08: POD 9
▪Labetolol Infusion 10ml/hour : ▪110/70 : atenolol /labetolol
24 hours /amlodepine
▪Atenolol /Amlodepine

▪Continued till POD 6

60
▪ VT 31 years old : 6 weeks
confirmed gestation
,seeking specialty care due
to previous adverse
pregnancy outcome
 ▪2 years prior she had induced PTVD ( 26
W ) for MASSIVE abruption leading to IUD
▪She has come for guidance .
▪Her baseline work up now
CBC : Hb : 10 g/dl , wbc : 8700 , platelets
170000, MCV : 65
▪She has no previous records but has not
been investigated after delivery

63
 Red flags for Abruption ?

64
▪Previous abruption is
the strongest risk factor
for abruption
▪Recurrence risks of 10-
to 15-fold higher
▪93-fold higher (95% CI
62-139) .
 ▪Hypertensive women have a five-fold increased
risk of severe abruption compared to normotensive
women
▪Antihypertensive therapy does not appear to
reduce the risk of placental abruption among
women with chronic hypertension

66
67
 Which antibodies ?
Lupus anticoagulant (LA)
▫Anticardiolipin antibodies
(ACL IgG and ACL IgM)
▪Others have such as
β2glycoprotein-I,
antiphosphatidylserine
antibodies, annexin, etc
may not be obstetrically
significant

68
 Obstetric Criteria
Three or more consecutive
spontaneous abortion before the 10th
week of gestation

One or more unexplained fetal death

at or beyond the 10th week of
gestation

Severe preeclampsia or placental

insufficiency (IUGR) necessitating birth
before the 34th week of gestation

69
Women with PAPS without a Women with PAPS with history of
history of thrombotic events thrombotic events (past or
(most women with RPL) present)

Prophylactic therapies such as Full anticoagulation with heparin

aspirin, heparin in pregnancy and 6 (or warfarin) in pregnancy and
to 8 weeks postpartum postpartum

70
Aspirin alone v/s Aspirin + Heparin
▪Recent metaanalysis shows that the combination of Aspirin +
Heparin is better than Aspirin alone in achieving live births in
women with recurrent pregnancy loss and antiphospholipid
antibodies
Mak A et al, Rheumatology (Oxford) 2010

71
Is Heparin + Aspirin really better?
▪The metaanalysis was based on data from five trials involving 334
patients across non uniform care platforms
▪Overall live birth rates were 74.27 and 55.83% in the combination
and aspirin alone groups
▫RR 1.301; 95% CI 1.040, 1.629
▫Number needed to treat is 5.6
▪There is no placebo group for comparison
▪Another metaanalysis showed that LMW heparin + Asprin does not
significantly improve birth rates. The benefits is present only with
unfractionated heparin
Zikas PD et al, Obstet Gynecol 2010
72
 Clinical Tips for using Heparin
▪There is controversy as to whether LMW Heparin is
effective in preventing recurrent pregnancy loss
▪Consider costs, convenience and compliance before
initiating therapy
▪Therapy should be started when fetal cardiac activity is
demonstrated and continued throughout pregnancy
and postpartum
▪Heparin in prophylactic doses needs to be stopped for
about 24 hours around the time of labor and delivery
73
 Clinical Tips for using Heparin
▪Heparin in prophylactic doses can not be
monitored and does not require monitoring by
coagulation parameters
▪Do a platelet count at 3 days, 1 week and
bimonthly when the patient is on heparin
▪Standard doses
▫Unfractionated heparin – 5000 units sc bd
▫Enoxaparin – 40 mg sc daily or in two doses
74
Ameena G2 P1(3Y back)
 Low risk mother
 38 W PROM for 12 hours
 Irritable uterus : cervix admits tip of finger , no effacement
 Misoprostol Sublingual 50mcg administered
 After 4 hours complained of acute pain and uneasiness
 PV : Cervix 1.5 cms 30 % effaced
 Second Misoprostol administered
 After 45 mins became fully dilated and taken to delivery table
Delivered and collapsed !!
▪Blue code initiated
▪Placenta delivered
with AMTSL
▪PROFUSE PPH
▪Wheeled to the OR
 Massive hemorrhage

ICU

Pelvic
IONOTROPES
OB HYST MTP Pack Uraemia TRALI Succumbed

DIC management

Dialysis

78
Amniotic Fluid
Embolism
Mechanism
POGS Annual CME
79
 80
POGS Annual CME

Diagnosis
 The presence of squamous cells in the pulmonary
arterial blood obtained from a Swan-Ganz catheter
once considered pathognomonic for AFE is neither
sensitive nor specific

 The monoclonal antibody TKAH-2 may eventually

prove more useful in the rapid diagnosis of AFE.
criteria for diagnosis of amniotic fluid
POGS Annual CME
81

embolism