10/15/2012

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Hemorrhage and DIC in pregnancy

Steven Fein, MD, MPH Hematologist and Oncologist

Baptist, South Miami, Homestead, Mariners, Doctors and West Kendall Baptist Hospitals

September 14, 2012

Speaker Disclosure

Steven Fein, M.D., has indicated that he has on the speakers’ bureau for Amag Pharmaceuticals and American Regent Pharmaceuticals. He has indicated that his lecture will include mention of investigational or off-label usage.

All conflicts of interest of any individuals who control the content of this CME activity, including faculty and members of the Continuing Medical Education Committee and the Continuing Medical Education Department, have been identified and resolved.

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Learning Objectives

Upon completion of this conference, participants should be better able to:

Define and identify clinically significant peripartum hemorrhage and disseminated intravascular coagulation (DIC).

Prescribe appropriate interventions for peripartum hemorrhage and DIC.

Implement strategies to consistently screen pregnant patients for iron deficiency to minimize the impact of peripartum hemorrhage.

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What we discussed during 2/2012

Anemia during pregnancy

Low platelets during pregnancy

Peripartum bleeding

Clotting during pregnancy

What we discussed during 2/2012

Anemia during pregnancy

Most pregnant women are iron deficient

Low platelets during pregnancy

Low platelets usually unimportant

Peripartum bleeding

Bleeding may cause DIC, need transfusions

Clotting during pregnancy

Use Enoxaparin for pregnant clotters

What we’re going to discuss

How to deal with bleeding during parturition

How to identify and deal with DIC during parturition

How to prevent severe anemia by infusing IV iron

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Better to be a bleeder than a clotter

Bleeders Clotters Young people

Hemophilia, VWD

Liver dysfunction

Renal dysfunction

Iron deficiency

Anticoagulants

Wine with dinner

Longevity

Older people

Clotting disorders

Infertility, miscarriages

Cancer, autoimmune dz, AIDS

Chronic inflammatory states

CAD, stroke, TIA, dementia

Venous thrombosis, varicose veins

Earlier mortality

How bleeding is prevented

Extrinsic clotting cascade

Intrinsic clotting cascade

Tissue factor/trauma triggers

Other clotting stiumuli

710-5-2-1 119810-5-2-1

Measured by PT INR Measured by aPTT

Vitamin K defic, cirrhosis, and warfarin affect PT INR

VWD, hemophilia, and anticoagulants affect aPTT

Lupus anticoagulant-clotting disorder assoc with high PTT

Case #1

18yo man hit in neck during a soccer game

now c/o dyspnea and neck pain

h/o hemorrhage during tonsillectomy

Plt 212,000

PT 12 secs; aPTT 64 secs

aPTT with mix 30 secs

What is the most likely diagnosis?

Answer: ?

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Case #1

18yo man hit in neck during a soccer game

now c/o dyspnea and neck pain

h/o hemorrhage during tonsillectomy

Plt 212,000

PT 12 secs; aPTT 64 secs

aPTT with mix 30 secs

What is the most likely diagnosis?

Answer: Hemophilia A (Factor VIII deficiency)

Factor deficiency

Delayed bleeding

aPTT with mix shows nearly full correction

Factor deficiency among intrinsic factors

Factor 12 defic does not cause bleeding

Factor 11 defic is auto recessive, Jewish people

Factor 9 defic (Hemophilia B) is X-linked

Factor 8 defic (Hemophilia A) is X-linked

Treatment of factor deficiency

FFP: all factors, but little fibrinogen

Cryoprecitipate:

Fibrinogen, Factor VIII, and VWF

Humate P: Factor VIII and VWF

Recombinate: Recomb Factor VIII

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Case #2

32yo man h/o spontaneous abortions, now 23 weeks pregnant with DVT

Plt 110,000

PT 12 secs; APTT 56 secs

aPTT with mix-->52 seconds

What is the most likely diagnosis?

Answer: ?

Case #2

32yo man h/o 2 spontaneous abortions, now 23 weeks pregnant with DVT

Plt 110,000

PT 12 secs; APTT 56 secs

aPTT with mix-->52 seconds

What is the most likely diagnosis?

Answer: Lupus anticoagulant (APLS)

Treatment of lupus inhibitor

Anticoagulation

During pregnancy use Enoxaparin

Chemotherapy or Rituximab

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Bleeding patients with normal coags Platelet dysfunction

Bleeding time not useful

Von Willebrand disorder

Very low platelet count (<20)

ITP, DIC, drug-induced

Platelet dysfunction

Inherited platelet dysfunction (rare)

Bernard-Soullier GP1b

Glanzman’s thrombasthenia GP2b3a

Acquired platelet dysfunction

aspirin, antiplatelet agents, uremia, MDS (older pts)

Von Willebrand Disorder

Bleeding tendency usually labeled VWD

Real VWD

Hereditary, autosomal dominant

History of epistaxis or menorrhagia

Low platelets with bleeding (not ITP)

Borderline high PTT (35-45 secs)

VWD type Problem Treatment

Type I Deficient VWF ddAVP (desmopressin)

Type II Dysfunctional VWF Humate P or cryoprecipitate

Type III Absent VWF Humate P

Case #3

30yo woman with easy bruising, epistaxis,

PMH: prior post-partum hemorrhage

Plt 250,000

PT 12 secs; aPTT 40 secs

Plt aggregation studies normal

What is the most likely diagnosis?

Answer: ?

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Case #3

30yo woman with easy bruising, epistaxis, menorrhagia

PMH: prior post-partum hemorrhage

Plt 250,000

PT 12 secs; aPTT 40 secs

Plt aggregation studies normal

What is the most likely diagnosis?

Answer: Von Willebrand’s disease

Treatment of VWD

Desmopressin=ddAVP

releases stored VWF

Helps Type I VWD (VWF deficiency)

Humate P: Factor VIII & VWF

Cryoprecipitate: Fibrinogen & VWF

What to do with abnormal CBC during 2nd trimester

Use CBC to screen for bleeding tendency

“mild” anemia HCT 30-35

test iron and TIBC (iron/TIBC=iron saturation)

“moderate” or “severe” anemia HCT <30

Test iron sat and consider hematology referral

Low MCV <82

Test iron sat and consider hematology referral

Low platelets: hematology referral

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What to do with abnormal CBC during 3rd trimester

Use CBC to screen for bleeding tendency

“mild” anemia HCT 30-35

test iron and TIBC (iron/TIBC=iron saturation)

“moderate” anemia HCT 22-30

Test iron sat and consider hematology referral

“severe” anemia HCT<22

Hospital admission and consider iron vs. RBC

Low platelets: hematology referral

What to do with abnormal CBC at term

Use CBC to screen for bleeding tendency

“mild” anemia HCT 30-35

test iron and TIBC (iron/TIBC=iron saturation)

“moderate” or “severe” anemia HCT 22-30

Test iron sat and consider hematology consult

Screen for bleeding tendency

Stratify risk for peripartum hemorrhage

Low platelets: hematology inpatient consult

Usually don’t need platelet transfusions

Why peripartum hemorrhage is important

5% of all pregnancies

>1 L blood loss at parturition

1L is a typical expansion of blood volume so that amount of volume loss is tolerated

Hypovolemic shock should be avoided

Don’t let bleeding get to 2L (40% volume)

Can use IVF to minimize risk of hypotension, but hemodilution may cause severe anemia

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1999-2008

FLORIDA MATERNAL MORTALITY

MORTALITY RATE 17 PER 100,000 LIVE BIRTHS

Goals for peripartum hemorrhage

Save lives

Decrease need for invasive procedures

Decrease use of transfusions

Decrease anxiety

Stratify risk for peripartum hemorrhage

Maternal hemorrhage task force

Anesthesia, Ob, Nursing, Transfusion svcs, Pharmacy, Lab, Respiratory

Do: Develop and implement a protocol for

maternal hemorrhage

Check:Monitor outcomes of MHP patients.

Debrief and assess communication

post hemorrhage.

Act: Track for

coagulopathies(INR), timeliness of arrival of blood and

PPH LOS.

Plan: Decrease morbidity and

mortality related to maternal

hemorrhage.

Maternal Hemorrhage

Plan

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Ob risk factors

Heme risk factors

No risk factors

How to treat peripartum hemorrhage

Identify those at risk for bleeding

Identify those who bleed more than 500mL

Try non-pharmacologic interventions

Try simple pharmacologic interventions

Consider blood product transfusions

Consider Recombinant Factor VIIa

Consider invasive procedures

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Usual interventions for bleeding

Oxycotin before delivery of placenta

Early cord clamping (<2 min)

Gentle traction, suprapubic countertraction

Fundal massage

Monitor volume of hemorrhage

Reasons for hemorrhage Intervention

Tone Uterine atony 95% Bimanual massage, meds

Tissue Retained tissue or clots

Remove placenta and clots

Trauma Laceration, rupture Identify and repair lacs or rupture

Thrombin Bleeding tendency ddAVP 20 mcg IV or presume DIC

Pharmacologic interventions for peripartum hemorrhage

Oxytocin IV infusion

Methergine q5 mins

Hemabate (prostaglandin F2 )

Misoprostol (prostaglandin E1)

DdAVP 20 mcg IV (desmopressin)

Amicar 2-4g IV bolus followed by 1g/hr

Recombinant Factor VIIa

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Hematologic causes of peripartum hemorrhage

Identify coagulopathy (abn coag studies)

PTT>40 secs may be a sign of VWD

PT INR>1.4 may be due to liver dysfunction

Low platelets antepartum not usually a bleeding risk unless <20

ITP, HELLP, or gestational thrombocytopenia

Low platelets peripartum could signal DIC

Low fibrinogen <200 usually means DIC

Who needs a blood product transfusion?

Treat severe bleeding with RBC transfusions

EBL>1500mL triggers Level 3 MHP

Try to minimize bleeding by “correcting” coagulopathy or treating presumed VWD

FFP 3-4 units (or 2 units per 4 units RBC)

Platelets not needed unless plt count<20

Cryoprecipitate or Humate P for VWD

Identify and treat DIC (cryoprecipitate and plts)

There is no proven ratio for massive transfusions

Massive hemorrhage pack 6:4:1 (RBC:FFP:plt)

History of transfusion

1800’s: spouse blood transfused for postpartum hemorrhage

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History of transfusion

1800’s: direct transfusions used for several medical conditions

History of transfusion

1900’s: Karl Landsteiner

Blood groups (ABO) identified by testing 5 people

Nobel Prize 1930

History of transfusion

1910’s: anticoagulants (citrate) enabled storage

1930’s: Charles Drew separated blood components

Director of American Red Cross

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History of transfusion

History of transfusion

Transfusions in 2012

Bleeding after trauma or surgery

Visible hemorrhage or hematoma

Peripartum bleeding

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What if you needed a transfusion?

Would you accept a transfusion without investigating the risks and benefits?

What questions do you have about blood? Reactions?

Infection?

Will it make me heal faster or slower?

Recombinant Factor VIIa

Issues with Recombinant Factor VIIa:

• Identify (or presume) and treat DIC first

• Low dose, typically 2mg IV

• Theoretical clotting risk

• Expensive

Invasive interventions for bleeding

Uterine artery embolization or ligation

Hysterectomy

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Causes of Peripartum DIC

Bleeding causes more bleeding

Placental abruption

Severe peripartum hemorrhage

Other important causes of Ob DIC

Fetal demise with delayed delivery

Ambiotic fluid embolus

Septicemia

What is DIC?

Disseminated Intravascular Coagulation

Clotting leads to bleeding

• Microthrombosis uses up fibrinogen

• Excess bleeding caused by

• Low fibrinogen

• Dysregulation of thrombinolysis

Non-OB causes of DIC

Clotting DIC trauma or sepsis

Bleeding DIC in APL or prostate cancer

How to diagnose DIC

Clinical scenario + lab testing

High suspicion if bleeding is excessive

Try to evaluate viscosity of blood

Can presume DIC in emergencies

Test stat CBC, aPTT, fibrinogen

If trending low plts and high aPTT, then DIC may be presumed

If low fibrinogen <200 DIC likely

High D-dimer nonspecific but supports dx

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Treatment of DIC

Address the underlying problem

infection, malignancy, bleeding

Platelet transfusion for bleeding or <20K

OK to transfuse for <50K for known DIC

FFP: repletion of clotting factors

3-4 units FFP at a time, unless massive transf

Cryoprecipitate: repletion of fibrinogen

10 units cryoprecipitate

Case #4

38yo woman with full-term pregnancy

History of menorrhagia

Now severe post-partum hemorrhage

Hgb 106; HCT 3018

plt 130k50k

PT 28 secs; APTT 50 secs; fibrinogen 50 mg/fL

Answer: ?

Case #4

38yo woman with full-term pregnancy

History of menorrhagia

Now severe post-partum hemorrhage

Hgb 106; HCT 3018

plt 130k50k

PT 28 secs; APTT 50 secs; fibrinogen 50 mg/fL

Answer: DIC

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Treatment of DIC

Address the underlying problem

infection, pregnancy, bleeding malignancy

Platelet transfusion for bleeding or <20K

FFP: repletion of clotting factors

Cryoprecipitate: repletion of fibrinogen

How to treat peripartum hemorrhage

Identify those at risk for bleeding

Identify those who bleed more than 500mL

Try non-pharmacologic interventions

Try simple pharmacologic interventions

Consider blood product transfusions

Consider Recombinant Factor VIIa

Consider invasive procedures

What can we do for bloodless pts?

Antepartum

Identify those who refuse blood transfusions

Identify those who are at risk for bleeding

Identify and treat those with iron deficiency

Peripartum

Blood conservation approaches to anesthesia and surgery

Recombinant Factor VIIa for severe bleeding

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What we’re going to discuss

How to deal with bleeding during parturition

How to identify and deal with DIC during parturition

How to prevent severe anemia by infusing IV iron

Minimize severity of anemia by treating iron deficiency

Identify iron deficiency before term

Iron saturation testing (Fe/TIBC) is not the same as hemoglobin testing

Maybe beneficial to treat iron deficiency even if normal or near normal Hgb

Severe iron deficiency common among young women

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Chewing ice is not just a habit

Symptoms of iron deficiency

Feeling tired and weakness

Palpitations

Headache

SOB with minimal exertion

Brittle hair and nails

Increased vulnerability to infection

Craving ice

Disturbed sleep, concentration, memory

Abdominal pain

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RBC size on a blood smear

Microcytic Macrocytic

Iron is the oxygen carrier

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Causes of iron deficiency

Not enough iron in

Malabsorption

Malnutrition

Acid suppression

Gastric bypass

Autoimmune disease

Too much iron out

Pregnancy

Chronic bleeding

Chronic wounds

Excessive phlebotomy

Chronic hemolysis-PNH

Most young women with anemia also have iron deficiency

Chronic bleeding causes iron deficiency

Most commonly menstrual bleeding (young) or GI/GU bleeding (older patients)

Iron deficiency anemia (IDA) may result from the combination of chronic bleeding and bone marrow dysfunction

Impaired iron absorption also common

How to treat iron deficiency Intervention Hemoglobin Iron

Address chronic or

acute bleeding

Stop decreasing

Oral iron supplement Weeks-months Slow

IV iron supplement Days-weeks Fast

RBC transfusion Hours Fast

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Transfusing iron deficient patients

Chronic bleeding causes iron deficiency

Anemia caused by bleeding and lack of Fe

Transfusion mainly repletes iron

Can substitute IV iron formulations

Need to identify cause of bleeding

Which is more effective?

Case #5

27yo young woman with prior twin gestation now 28 wks pregnant, tired, denies visible bleeding

Exam: P 90 SBP 110 not orthostatic

Cup of ice on bedside table

Data: Hgb 7 HCT 22 MCV 80

What is the most likely cause of anemia?

Answer: ?

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Case #5

27yo young woman with prior twin gestation now 28 wks pregnant, tired, denies visible bleeding

Exam: P 90 SBP 110 not orthostatic

Cup of ice on bedside table

Data: Hgb 7 HCT 22 MCV 80

What is the most likely cause of anemia?

Answer: Iron deficiency

Intravenous iron infusion

Iron sucrose 400mg IV daily x 2 days

2-3 hour infusion

Pregnancy Class B

No premeds needed

No test dose needed

Clinical Pearls

Instructions: Please make this one of your conclusion slides. Please insert 2-3 key learning “take away” messages that

participants will be able to incorporate into their clinical practice.

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Baptist Children’s Hospital Baptist Hospital Doctors Hospital

Baptist Cardiac & Vascular Institute

Homestead Hospital Mariners Hospital

West Kendall Baptist Hospital

Baptist Outpatient Services

South Miami Hospital

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