The Clot Thickens

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The Clot Thickens

• Dr Sam Yuen
• Department of Haematology
• John Hunter Hospital

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MM 29 yo G1P0, 28 weeks 2

• Expected due date 9/7/05.
• Uncomplicated antenatal follow up at Maitland
  Hospital.
• Initial follow up
• BP 100/60
• A Rh-ve
• Rubella immune, Hepatitis B/C negative.
• PMHx
• Mild asthma with NSAID sensitivity.
• Smoker 5 cigarettes/day.
• Nil regular medications.

3

• 18/4/05
• Onset of epigastric pain
• Nausea and vomiting
• No headache or visual symptoms
• BP 165/95
• Mild RUQ tenderness
• Reflexes are normal
• Mild pedal oedema

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Investigations

• FBC
• Hb 130 x 109/L, WCC 15.1 x 109/L, Plt 222 x109/L
• LFT
• Bilirubin 12umol/L
• GGT 9U/L, ALP 183 U/L, ALT 124 U/L, AST 205 U/L
• Urate 0.25 mmol/L
• Urinalysis no protein

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Initial assessment at JHH 19/4/05

• Clinically well
• BP 120/75
• Mild RUQ tenderness
• Normal reflexes
• Urinalysis NAD
• CTG/mobile fetal U/S unremarkable
• Investigations
• LFTs ALT 190 U/L, AST 272 U/L
• Urate 0.28 mmol/L
• Hb 116 x 109/L, Plt 150 x 109/L
• Kleihauer test negative
• Rx betamethasone

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What is the differential diagnosis?

• Preeclampsia
• Acute fatty liver of pregnancy
• HELLP
• Viral hepatitis

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Progress 20/4/05

• Epigastric pain settled
• BP 120/80
• Reflexes normal
• U/A no proteinuria
• Abdominal U/S normal study
• Viral hepatitis serology negative
• LFT
• Bilirubin 6 umol/L, gGT 178 U/L, ALP 178 U/L, ALT
  98 U/L, AST 65 U/L

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Progress 21/4/05, 0025hrs 0415hrs

• Severe epigastric pain radiating through to back
• Headache/nausea
• BP 130/80 190/110
• Sats 99 RA
• Afebrile
• Brisk reflexes
• Investigations
• Hb 118 x 109/L WCC 17.9 x 109/L Plt 196 x 109/L
• Amylase 57 U/L, lipase 175 U/L
• ALT 235 U/L, AST 249 U/L
• Coags, urate, UEC normal
• Rx 2.5mg hydralazine IVI, pethidine for analgesia
• Transferred to delivery suite

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Progress 21/4/05, 0805

• Continued epigastric pain
• Nil relief with ranitidine/mylanta/pethidine
• BP 146/78
• Brisk reflexes, no clonus
• U/A trace protein and leucocytes
• Decision made for emergency LUSCS

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Operating Theatre, 21/4/05 1000hrs

• LUSCS
• Blood stained ascitic fluid.
• Blood staining and clots in amniotic fluid ?
  Placental abruption.
• Male infant delivered breech extraction.
• Some difficulty achieving haemostasis.
• BP
• 100/50
• 70/40 88/55 (b/w 1130hrs 1230hrs) Hb 71
• 116/76 upon completion of OT 1415hrs
• Estimated blood loss 800mls intraoperatively.
• Surgical drain 400mls post operatively.
• Haematuria noted in IDC post operatively.

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Post-operative bloods, 21/4/05 1345hrs

• FBC
• Hb 67 x 109/L WCC 23.3 x 109/L Plt 34 x 109/L
• Blood film anaemia, polychromasia, neutrophilia
  with toxic change. Thrombocytopaenia.
• Coags
• PT gt 100 sec APTT 49 sec
• Fibrinogen lt 0.3 g/L
• LFT
• Bilirubin 60 umol/L
• ALP 139 U/L ALT 2506 U/L AST 4523 U/L
• UEC
• Na 140 mmol/L K 3.4 mmol/L HCO3 19 mmol/L Ur 5.8
  mmol/L Cr 98 mmol/L

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Diagnosis

• HELLP
• Haemolysis
• Elevated liver enzymes
• Low platelets
• DIC

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Initial management

• Volume replacement
• Transfused 2 units PCC
• 4L crystalloid
• DIC management
• 10 units of cryoprecipitate
• 4 units of platelets (pooled)
• 4 units of FFP

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Transfer to ICU 21/4/05, 1630hrs

• Clinical status
• BP 94/55
• PR 88
• Sats 100 3LO2
• BSL 8.2 mmol/L
• Total input 1680ml (since OT)
• Total output 660ml from drain (no urine)
• Abdomen soft
• U/S abdomen no evidence of subcapsular haematoma

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ICU progress 22/4/05, 0300hrs

• Abdominal pain and distention
• BP 110/80, PR 125
• Surgical drain 1570mls since OT
• Small amount of PV blood loss
• No urine output
• Hb 70 x 109/L WCC 15 x 109/L Plt 25 x109/L
• PT 16 sec APTT 35 sec fibrinogen 1.1g/L
• UEC Na 138 mmol/L K 5.7 mmol/L Cl 103 mmol/L HCO3
  22 mmol/L Ur 7.7 mmol/L Cr 159 mmol/L
• BSL 11 mmol/L

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Issues

• Haemoperitoneum
• Lack of improvement in Hb disproportionate to
  drain/PV blood loss
• No evidence of haemolysis on blood film
• Ongoing coagulopathy secondary to DIC
• End organ damage (secondary to hypotension/microan
  giopathy)
• Renal failure
• Hepatic ischaemia/necrosis subcapsular
  haematoma?

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Exploratory laparotomy 22/5/05, 0530hrs

• Haemoperitoneum clots and blood in upper
  abdomen.
• Subcapsular liver haematoma drained.
• Liver subsequently packed.
• Slight ooze from uterus.
• Abdomen left open
• Given further blood product support
• Cryoprecipitate aiming for fibrinogen gt 2.0
• Platelets
• Packed cells
• FFP
• Returned to ICU ventilated intra-abdominal
  pressures monitored.

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The following 24 hrs

• Returned to theatre for exploratory laparotomy
  twice because of ongoing haemodynamic instability
  and increased intra-abdominal pressures.
• Evacuation of peritoneal blood, repacking of
  liver.
• 6mg rVIIa administered intraoperatively because
  of continual ooze.
• 2nd dose rVIIa given postoperatively because of
  large blood loss from drains (1700ml).
• 25/4/05 removal of packs
• New posterior lobe liver haematoma
• Coags and fibrinogen normalised.
• Platelets 60 given platelet support.
• Given further dose of rVIIa.

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Progress

• Closure of abdomen and cessation of bleeding
• Ongoing problems
• Catabolic state
• Ascites and pleural effusion
• Renal failure requiring dialysis
• Pneumonia and line sepsis.
• No thrombotic sequelae
• Eventually dialysis independent and discharged on
  20/5/05.

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HELLP

• Haemolysis, Elevated Liver enzymes, Low
  Platelets.
• 1 in 1000 pregnancies.
• 10-20 of women with severe preeclampsia/eclampsia
  .
• Majority of cases between 28-36weeks gestation.
• 30 of cases occurring postpartum.
• Signs of DIC occur in approximately 20 percent of
  patients.
• marked elevation of serum aminotransferases are
  not typical of HELLP (marked elevation may
  indicate hepatic infarction/subcapsular
  haematoma).
• DDx
• Hepatitis, appendicitis, gallbladder disease,
  gastroenteritis
• ITP
• TTP/HUS
• Acute fatty liver of pregnancy

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HELLP Diagnosis

• No consensus regarding degree of laboratory
  abnormalities diagnostic of HELLP.
• Existence of preeclampsia and all of the
  following
• Microangiopathic haemolytic anaemia
• Platelet count lt 100000 cells/microL
• Serum LDH gt 600IU/L or total bilirubin gt1.2mg/dL
• Serum AST gt 70IU/L
• Women who do not meet all above laboratory
  abnormalities are considered to have partial
  HELLP syndrome.

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Blood film
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What is rVIIa?

• Recombinant clotting factor
• rVIIa induces thrombin generation and haemostasis
  by two mechanisms
• At the site of injury through the formation of
  complexes with exposed tissue factor (TF
  dependent effect)
• By directly activating FX on the surface of
  activated platelets (TF independent effect)

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Normal Haemostasis
II
X

• TF/VIIa activates IX
• IXa and VIIIa adhere to activated platelet
  surface
• VIIIa/IXa further activates X
• Xa/Va activate large amounts of IIa THROMBIN
  BURST
• Development of fibrin forming clot

VIII/vWF
TF
VIIa
Xa
IIa
Va
VIIIa
TF-Bearing Cell
XI
XIa
TF
V
Va
VIIa
IX
Platelet
II
IXa
X
IIa
Xa
XIa
VIIIa
IXa
Va
Activated Platelet
Fibrinogen
Fibrin
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Mechanism of Action in New Indications
II
IXa
X
IIa
Xa
VIIIa
IXa
Va
IIa
Activated Platelet
II
IXa
X
IIa
Xa
rFVIIa
VIIIa
IXa
Va
Activated Platelet
Va
rFVIIa
IIa
Xa
II
X
New Indication include trauma, cardiothoracic
surgery, liver surgery, thrombocytopenia, etc
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The use of rVIIa in HELLP

• 4 documented cases of pregnancy associated
  spontaneous liver haematoma.
• Laparotomy in 2 patients with liver packing.
• 1 patient suffered eclamptic seizures and
  survived a cardiac arrest on presentation.
• Abdominal compartment in 1 patient managed with
  percutaneous decompression tube.
• 1 patient managed without laparatomy. Given rVIIa
  because of refractory postpartum vaginal
  bleeding.
• All continued to bleed despite blood product
  support.
• rVIIa used as last resort

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Use of rVIIa in HELLP

• Outcomes
• Significantly contributed to achieving
  haemostasis and reversal of coagulopathy.
• No evidence of thromboembolic sequelae in any of
  the cases.
• 1 patient suffered anoxic brain injury as a
  result of cardiac arrest. Ventilatory support
  withdrawn by family request. Post mortem did not
  show evidence of systemic thrombosis.