This document discusses hematological abnormalities in pregnancy induced hypertension (PIH). It begins with an introduction to PIH and its classification. It then summarizes the various hematological changes that can occur in PIH including thrombocytopenia, anemia, and coagulation changes. Three case reports are presented that demonstrate severe hematological complications of PIH including HELLP syndrome, disseminated intravascular coagulation (DIC), and refractory anemia. The document discusses the epidemiology, pathophysiology, clinical presentation, and management of HELLP syndrome and DIC. It also notes that hyperferritinemia can occur in PIH and eclampsia.

1. HEAMATOLOGICALABNORMALITIES
IN
PREGNANCY INDUCED HYPERTENSION
PROF. HALEEMA A. HASHMI
Liaquat National Hospital, Karachi

2. INTRODUCTION
Pregnancy specific condition associating pregnancy
induced hypertension and proteinuria may present
diverse haematological features, varies from normal
laboratory test to severe thrombocytopenia due to
platelet activation and consumption and / or
anaemia.
Hypertension complicates 10 – 15% pregnancies, 15 –
20% maternal mortality .

3. PLAN
 Introduction of PIH, ACOG Classification &
Pathogenesis.
 Haematological Changes in PIH
 Case Reports on Haematological Complications,
HELLP, DIC & Anaemia.
 Epidemiology, Pathophysiology Clinical Presentation,
Complication & Management of HELLP & DIC.
 Rare Association of Haematological Disorders with
PIH.
 Conclusion.

4. Classification of ACOG
PIH
 Hypertension is defined as Diastolic B.P. of
atleast 90 mmHg
 Systolic B.P. of atleast 140 mmHg
 Rise in Systolic > 30 mmHg
 Rise in Diastolic > 15 mmHg
 Occur after 20 weeks of gestation
 Return to base line postpartum

5. Hypertension in Pregnancy
 Hypertension without Proteinuria
 Pre-eclampsia – Hypertension with
proteinuria
 Eclampsia – Pre-eclampsia with seizures
 Coincidental Hypertension (HTN)
 Pregnancy aggravated HTN
 Superimposed PET
 Superimposed Eclampsia

6. PATHOGENESIS
Failure of 2nd wave of trophoblast invasion

 Blood flow in spiral arterioles

Placental bed Ischaemia

Stimulation of Macrophages

Liberation of TNF

Endothelial damage / dysfunction

In PIH = PGI2 < TXA2 = Vasospasm

7. 7

8. Haematological Changes in PIH
A. Numerical & Functional Platelet
Abnormalities.
 Platelet dysfunction & thrombocytopaenia –
50%
 Platelet consumption, activation, aggregation,
microangiopathic haemolysis.
 Sign of severe / aggravating PET

9. Haematological Changes in PIH
B. Alterations of Haemoglobin & Erythrocytic
Parameters
 Haemo-concentration ↑ HCT
 Due to ↑ endothelial permeability
 Microangiopathic, Hemolytic anaemia

10. Haematological Changes in PIH
C. Coagulation Changes
 Coagulation cascade activated
 Pre-eclampsia itself is a highly thrombotic and
procoagulant state with platelet activation and
consumption, thus promoting thrombin formation,
fibrin formation & destruction.
 Increased levels of thrombin- Antithrombin III (TAT)
complexes & PAI-1
 Fibrinogen, antithrombin III and PAI-2 are reduced

11. Haematological Changes in PIH
C. Coagulation Changes
 Decrease of Protein-C & S natural anticoagulant &
ATX III
 D-Dimers ↑ (Severe form of PET)
 Fibrin monomers not increased
 DIC associated with IUGR
 ↑ level of factor VIII antigen
 ↑ level of thrombomodulin

12. Summary of Haematological
Abnormalities in PIH
 Thrombocytopaenia with signs of medullar
regeneration younger platelets present
 No difference in W.B.C. differential count, Hb
level or erythrocyte parameters
 Platelet aggregation increased (CD41, CD61),
adhesion [CD42a, CD42b] and activation
[CD63, CD62P]

13. Comparison between the level of expression of platelet surface
markers in patients with preeclampsia (red) and controls (white).

14. Case Report I
21 year old gravida 1, para 0, Referred from A.M. Hospital.
History:
 Duration of gestation 31 weeks
 Jaundice, fever, vomiting for 10 days
 Hypertension x5 weeks irregular antihypertensives
Examination:
B.P. 140/80, Pulse 120/min, Tachypnoeic, Reflexes Brisk, HOF
= 28 weeks, No fetal heart
Vaginal Examination:
Not in Labour Cont.

15. Laboratory Investigation Data
 Hb = 9 gm/dl
 TLC = 12.4 x 109/L
 Platelets = 100 x 109/L
 PT = 44/9 Sec
 APTT = 92/25 Sec
 Urea = 49 mg %
 Uricacid = 10.9 mg %
 Creatinine = 3.15 mg%
 Na = 125 mmol / lit
 K = 5.8 mmol / lit
 HCO3 = 18 mmol / lit
 Serum Proteins = 5.3 gm %
 S. Albumin = 2.2 gm
 S. globulin = 3.10 mg%
 AG Ratio = 0.73
Cont.

16. Laboratory Investigation Data
 Hepatitis E.V = Non-Reactive
 Hepatitis bsAg = Non-Reactive
 Anti HCV = Non-Reactive
ABGs
 PH = 7.27
 HCo3 = 17.7 mmol / lit
 Po2 = 95.0 mmHg
 Serm Bilirubin = 11.82 mg %
 Indirect = 9.67
 Direct = 1.85
 SGPT = 451 unit / lit
 Alkaline Phosphatase = 717 unit/lit
 Serum fibrinogen = 91 mg
 FDP > 20
 Hepatitis A / V = Non-Reactive

17. What is the Diagnosis?

18. Management
Provisional Diagnosis PIH + Jaundice + Coagulation Defect +
Sepsis (HELLP)
 ICU care
 Termination of pregnancy with PGE2 – No response in 24
hours
 Condition deteriorated LSCS done – Macerated still born
male baby delivered
 Blood loss 1000 cc
 3 units of packed cells 24 units of FFPS + 6 units
cryopreciptate & 1 mega unit of platelet transfused
 Urine output gradually reduced urea creatinine ↑  Dialysis
done.
 B.P. dropped and after 48 hours patient expired.

19. Epidemiology HELLP Syndrome
 Incidence 4.5/1000 pregnancies 5 – 10% of
pregnancies with pre-eclampsia.
 30 – 50% with eclampsia in child bearing
female.

20. PATHOPHYSIOLOGY
Placental Ischemia

Endothelial dysfunction

Platelet aggregation

Altered ratio of Prostacyclin (PGI2) & Thromboxane

Thrombin – Induced activation of coagulation cascade

Haemolytic Anaemia

Multi-organ Micro-vascular Injury

21. Clinical Presentation
 Third Trimester presentation or with in 7 days
postpartum.
 Non specific symptoms – fatigue, malaise
 Rt. upper quadrant pain, nausea, vomiting Headache,
confusion 30 – 90%, irritability 30 – 60%.
 Hypertension 15 – 50% cases
 Visual changes in 17%.
 Eclampsia 1 in 2000 Pregnancies in U.K.
 Intrapartum 22%
 Antepartum 34%
 Postpartum 44%

22. Investigation
CBC: Anaemia, Thrombocytopaenia <100,000 /
mm3
Peripheral smear  helmet cell, bur cells
Shistocytes (microangiopathic Haemolysis)
LFTs ALT twice than normal
LDH Markedly elevated (> 600 u/l)
Bilirubin > 2 mg/dl

23. Complications
Maternal
 Subcapsular haematoma and liver rupture
 Abruptio placentae
 DIC
 Severe postpartum haemorrhage
 Stroke, cerebral haemorrhage
 Renal failure

24. Complications
Fetal
 Prematurity
 Placental insufficiency due to
 PIH
 IUGR
 Neonatal Intraventricular Haemorrhage

25. Management
 Medical & obstetrical emergency with maternal
mortality of 1 – 2% and fetal mortality of 10 – 30%
 > 34 weeks  Immediate delivery
 < 34 & 27 weeks – delivery within 48 hours after
medical stabilization
 < 27 weeks: conservative depending on response
 DIC  Conservative treatment contraindicated.
 Glucocorticoid to promote fetal lung maturity
 High dose for maternal benefit, high versus repeated
doses.

26. DIC in Pregnancy Induced Hypertension
 DIC is one of the most common and clinically
important acquired disorders of hemostasis.
 Sibai etal has reported 7% patients with severe pre-
eclampsia has developed DIC.
 Severe PIH with Abruptio
 Eclampsia – uncontrolled leads to DIC

27. The Mechanism of Disseminated
Intravascular Coagulation.
Systemic activation of
coagulation
Intravascular deposition of
fibrin
Depletion of platelets and
coagulation factors
Thrombosis of small and
midsize vessels and organ
failure
Bleeding

28. Pathogenetic Pathways Involved in Disseminated
Intravascular Coagulation.

29. DIC in PIH
Pathogenesis
 Generation of Thrombin
 Defect in inhibitors of Coagulation
 Fibrinolytic Defect
Laboratory Diagnostic Criteria
 Platelet count: less than 100,000/mm3
 Prolongation of clotting time PT & APTT
 FDP ↑ in plasma
 Low plasma levels of Antithrombin III
 Deficiency of Vit K.

30. DIC in PIH – Management
A. Treatment of Primary cause
 Control of Hypertension
 Termination of Pregnancy
B. Supportive
 Anticoagulants – Heparin No RCT
 Interruption of coagulation process
 Low dose 300 – 500 U/hour Infusion
 LMWH can also be used

31. DIC in PIH – Management
C. Coagulation Inhibitor
Anti thrombin III – No RCTs
D. Platelets & Plasma Transfusion
For operative intervention
E. Antifibrinolytic Agents = Not recommended
F. Administration of Recombinant Factor VII a
G. Protein C Concentrates

32. Case Report II
Mrs. G.A. 30 years, G1, Para 0. Referred from NICVD, No. ANC.
History:
 Gestational Amenorrhoea 32 weeks
 Severe breathlessness x 5 days
 Admitted at NICVD – Hb 5.0 gm
 Blood transfusion given & referred to LNH
Examination:
Pallor + +, Severe Breathlessness, BP 170/95 mmHg, Pulse 180/min,
Respiratory rate 40/min, Temp 102 oF, HOF= 32 weeks.
Vaginal Examination:
No Signs of Labour
Cont.

33. Laboratory Investigation Data
 Hb = 5.0 – 8.0 gm/dl
 Group = O +ve
 RBS = 102 / m
 PT = 34/11
 APTT = 110/31
 TLC = 30 x 109 / L
 Platelets = 289,000 /m3 
15,000
 INR = 4.0
ABGs
 Severe Metabolic acidosis
 Urincacid = 8.5
 SGPT = 45
 Urea = 27
 Creatinine = 1.3
 Cl = 102 mmol/L
 Na = 141 mmol/L
 K = 4.3 mmol/L
 HCO3 mmol/L
 Blood Culture  Acino bacter
 Final Diagnosis  PIH &
Anaemic Cardiac failure
Cont.

34. Management
 Blood & Blood Products Transfused
 6 units Packed Cell
 6 units FFP
 6 units Platelets given
 Emergency LSCS done same day
 Gradually patient deteriorated & went into
MODs & Expired after 3 days.

35. Case Report III
32 years old Para 4, Admitted in Gasping condition
through ER, SVD at S.A. Clinic of an IUD fetus.
Patient became breathless & started to bleed vaginally
and referred to LNH in gasping condition, intubated.
Past H/O High B.P, Oedema & Abruptio placenta
O/E:
 Patient very pale
 Pulse 120/m, O2 saturation 60%
 Uterus 18 weeks, size, os open, bleeding + +
 CPR done – revived Cont.

36. Laboratory Investigation Data
 Hb = 2.7
 PCV = 9.1%
 Plateets = 36,000
 TLC = 18.6
 Urea = 91
Shifted to O.T.
Cardiac arrest occurred
Could not be resuscitated
 Diagnosis = DIC due to massive PPH secondary to
PIH & Abruptio
 Creat = 1.2
 Cl = 100
 Na = 13.6
 K+ = 6.9
 HCO3 = 7
 PT
 APTT / Prolonged

37. Hyper Ferritinaemia in Pregnancy
Induced Hypertension and Eclampsia
 Significant hyperferronaemia and hyperferritinaemia
in PIH & eclampsia attributed to altered liver
function or intravascular haemolysis resulting in
release of Iron from RBCs in eclampsia [P<0.01 <
0.05] significant elevation noted.
 ? Placental ferritin from placental damage due to
PIH.
Ref: Raman L, P Washe etal, J. Post gaud Med. India

38. HELLP Syndrome with Posterior
Reversible Leukoencephalopathy
 Rare association, related to hypertensive
encephalopathy, eclampsia MRI shows hyper
intense signal alteration in T2 weighted
images on the post lobe, basal ganglia & brain
stem.
 Clinical features are headache or blindness
(transient)
Ref: E: Marano etal, Neurol SCi (2003) 24, 82 – 84.

39. Brain MRI, axial T2-weighted images.
a. Spin echo sequence a few days after the generalized tonic-
clonic seizure shows bilateral, asymmetric hyperintensities in
the subcortical parieto-occipital white matter.
b. Fast spin echo, two-dimensional image six months later
reveals normal findings

40. Thrombophilia & Pre-eclampsia
 Case Control Study: found both acquired
thrombophilia and FV Laden Prothrombin gene
mutation associated with pre-eclampsia.
 Pub med 16 studies identified relationship between
heterozygous, FVL & PET.
 FVL found in 4 – 26% of patients with PIH
Kupfermin, ACA & MTHFR mutation associated
with SPE Proteins deficiency & prothrombin gene
mutation.
Ref: Hossain. N. Shamsi T. etal “Frequency of Thrombophilia in patients with
adverse Pregoutcome”. JPMA, 2005, 55(6), 245-7

41. Effect of Haematological Profile of
mothers with PIH and their Infants
 Maternal blood & Cord blood tested from both PIH &
Control groups at birth.
 Hb, TLC, DLC, Platelet Count
 Red Cell indicies, PCV, MCV, MCH & MCHC
 Peripheral blood smear tested
Maternal Effects:
 MCH, MCHC & Platelets were lower in PIH group
Ref: Sandhya Siva Kumar, etal, Indian Journal of Paediatrics, July,
2007, Vol. 74; 623 – 625.

42. Effect of Haematological Profile of mothers
with PIH and their Infants
Neonatal Effects:
 Platelet count in infants of PIH mother significantly low, particularly
in preterm babies.
 Number of nucleated RBCs, in peripheral smear of PIH affected
babies 7.38/100 WBCs as compared to 1.72 / 100 WBCs – controls.
 Polychromatic cells and target cells more in PIH babies than controls
 Hb no difference in PIH and control group
 MCV higher in babies born to PIH mothers
 Neonatal complications like sepsis, NET colitis
 Neutropaenia noted in infants of mother with PIH than controls.
Ref: Sandhya Siva Kumar, etal, Indian Journal of Paediatrics, July, 2007, Vol. 74; 623 – 625.

43. CONCLUSION
 PIH represents an important pathology in pregnancy affecting
maternal & fetal prognosis & outcome.
 Platelets play a central role in Pathophysiology of PIH and
current data suggests an altered functional status.
 Signs of medullar regeneration is represented by younger
platelets.
 Increased platelet aggregation (DC4 – CD62), adhesions
(CD2a – CD42b) and activation (CD63 – CD62b) noted in
PIH.
 Higher number of risk factors, lower platelet count.
 No significant difference in W.B.C., DLC, Hb levels or
Erythrocyte parameters.