Interesting Case

1
Interesting Case

• October 18, 2005

Roni J. Bollag
2
CASE HISTORY
HPI 29 year-old G6P4014 admitted for
preeclampsia and thrombocytopenia. Induction on
HD2 _at_ 383, AROM, vaginal delivery of healthy
baby girl (2910 g). Subsequently, patient
transfused with platelets for decreasing platelet
count. PMH (1) Asthma (2) Chronic
hypertension (3) History of histoplasma
(4) History of sputum-positive MAI (5) Carpal
tunnel syndrome (6) History of psychosis (7)
History of depression (8) History of
anxiety (9) Gastroesophageal reflux
disease (10) Type A1 gestational diabetes PSH
colposcopy with LLETZ conization for high-grade
SIL (97) SH ? tobacco, ? THC ROS ?
headache, ??chills, ??nightsweats, ? lochia, ? D
vision, ? CP/SOB, ? N/V
3
VITAL SIGNS T afebrile P80s R20
BP150-130/110-80
LAB
11.5
16.1 68
946 AM 708 PM 1247 AM 1001 AM
32.5
AST 45 ALT 14 AP 161 (H) BUN
7 Cr 0.8
11.0
14.0 29
32.3
10/3/05 10/4/05
2 Units platelets transfused
52,000 platelets
7.1
23.4 12
20.2
4
DIAGNOSIS HELLP HOSPITAL COURSE
Blood products Pharmacy

• 6 units platelets / 2 U PRBCs (10/4/05)
• 3 pheresis platelets (10/4/ - 10/05/05 PM)
• 10-pack platelets (10/7/05)
• 1 pheresis platelets (10/8/05)
• 4 units platelets / 2 U PRBCs (10/9/05)
• 2 pheresis platelets (10/10/05)

Insulin drip, demerol, prednisone Haldol
(agitation) increase prednisone dexamethasone
medrol dose pack medrol dose pack (d/c
prednisone)
10/11/05 mental status changes tonic clonic
seizure transfer to NSICU with Hem/Onc consult
5
NEW DIAGNOSIS TTP
TREATMENT PLASMA EXCHANGE q/DAY
6
11.0
11.5
13.3 250
8-18-05
16.1 68
10-3-05
32.2
32.5
10.9
11.6 182
6.6
9-22-05
32.5
21.3 9
10-4-05
19.1
8.5
24.5 182
10-5-05
Abnormal RBCs
23.6
6.0
25.0 8
10-8-05
16.6
6.7
31.8 5
10-11-05
18.7
10.8
48.2 14
10-12-05
30.5
8.4
77.0 10
10-13-05
24.3
7
(No Transcript)
8
(No Transcript)
9
Other findings of interest
Direct Coombs Test negative (10/11/05) Haptoglob
in lt 0.6 mg/dl (10/10/05) LDH elevated (entire
hospital course) CT (head) no acute process
(10/11, 10/12/05) Ophthalmology retinal
hemorrhage (on admission)
10

• Night of 10/13/05
• upper GI bleeding with coffee-ground emesis
• patient became hypotensive, then stabilized with
  NS volume resuscitation
• Hb dropped from 10.6 to 9
• Patient suddenly became hypotensive and pulseless
• aggressive resuscitation unsuccessful
• Cause of death GI bleed, possible cardiac
  tamponade 2o to TTP

11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
Echocardiogram (10/13/05) no acute process
16
(No Transcript)
17
Thrombotic thrombocytopenic purpura
An 18 year old girl presented with abrupt onset
of fever, anemia, renal dysfunction, CNS
impairment and cardiac failure. She died 2
weeks later.
Moschcowitz, E. Arch Int Med 1925 3689-93.
18
(No Transcript)
19
(No Transcript)
20
Thrombotic thrombocytopenic purpuraDemographics

• Incidence 1100,000 - 1500,000
• Malefemale 12
• Age
• Most common in 30-40 year olds
• 90 of patients 60 years old
• No racial differences
• No seasonal difference

21
Clinical Findings in TTP

• Microvascular thrombi MAHA
• Normal coagulation
• Thrombocytopenia (lt 20,000/µl)
• Anemia lt 10g/dl
• Reticulocytosis
• LDH
• Indirect bilirbuin
• Haptoglobin
• Pentad of symptoms

22
Pentad of TTP
23
Alternative diagnoses of patients who have
clinically suspected TTP/HUS

• Apparent after the plasma exchange has begun
• Autoimmune disorders
• Systemic lupus erythematosus
• Scleroderma
• Anti-phospholipid antibody syndrome
• Sepsis
• Malignant hypertension
• Heparin-induced thrombocytopenia/thrombosis
• Disseminated malignancy

24
Presentations of TTP/HUSThrombotic
microangiopathy

• Idiopathic
• No apparent etiology or associated condition
• Drug-induced
• Allergic Quinine, ticlopidine
• Dose-related Mitomycin, gemcitabine, cyclosporin
• Pregnancy/postpartum
• Diarrhea-associated
• Bone marrow transplantation
• Congenital

25
TTP in pregnancy

• (1) GI complaints often initial sign
• (2) preeclampsia (hypertension) often present
• (3) most common at term with progression
  post-partum
• (4) severe neurologic abnormalities and renal
  failure
• (5) disseminated microvascular thrombosis in
  absence of plasma exchange

George, Curr Opin. Hematol. 10339-344 (2003)
26
TTP in Pregnancy

• risk increases near term and post-partum
• accounts for 10 of all TTP
• decreased ADAMTS-13 activity and increased plasma
  vWF in 2nd / 3rd trimesters
• difficult to distinguish TTP / HELLP syndrome

27
TTP vs HELLP in Pregnancy

• TTP often presents before 24 weeks (gt50)
• HELLP rare in 1st half of pregnancy

• Antithrombin III by 1 S.D. in preeclamsia
• ATIII never affected in TTP
• hemolysis in HELLP often mild
• marked hemolysis and reticulocytosis in TTP
• TTP in 1/25,000 pregnancies HELLP in 1/100

28
(No Transcript)
29
vWF

• Multimers
• Made in megakaryocytes and endothelial cells
• Stored in platelet alpha granules and
  Weibel-Palade bodies of endothelial cells
• Ultralarge molecule cleaved to smaller subunits
  by protease ADAMTS-13
• ULVWF highly adhesive to platelets

30
vWF, Proteolysis, and Platelet Adhesion
31
von Willebrand Factor Multimers
120 nm
Adapted from Fowler et al, J Clin Invest
761491-1500, 1985
32
(No Transcript)
33
Treatment

• Plasma exchange
• removes antibody
• restores ADAMTS-13
• improves mortality rate to 10 20
• daily for 1-2 weeks
• Hemodialysis if kidney fails
• Plasma infusion if exchange not available
• Corticosteroids for non-responders

34
Summary

• Lab diagnosis of TTP
• Thrombocytopenia
• Microangiopathic anemia
• Schistocytes
• Increased LDH due to tissue necrosis
• Rule out other causes of MAHA
• Treatment Urgent plasma exchange