Heparin Induced Thrombocytopenia and Thrombosis

1. Weekly Death Round
DR. BEKA ABERRA
INTERNAL MEDICINE RESIDENT
R1

2. Outline of Presentation
1. Identification
2. History and Physical Examination
3. Progress of the patient
4. Circumstance of the death
5. Comments
6. Discussion
7. Take home message
8. References

3. Identification
NAME - T.Z
AGE - 45
SEX - MALE
ADDRESS - OROMIA,GOBA
MARTIAL STATUS - MARRIED
DOA - 06/02/2010 E.C
DOD - 19/02/2010 E.C

5. Medical History at ER [02-03/02/2010]
This is a 45 y/o M patient who is a diagnosed patient with SCC of the right inguinal
region with vertebral bone Metastasis on his 3rd Chemo [cisplatin/paclitaxel -
Q21days] and Radiotherapy (palliative) @ TASH over the past year; Paraplegic
patient 20 to Compressive Myelopathy 20 to Vertebral Metastasis 08 month.
Presented with change in mentation of 02 weeks duration, with failure of
communication, Low Grade Intermittent Fever, Easy fatigability, Loss of appetite and
Unquantified amount of weight loss.
Associated with a Gradual Decrease in Urine output and generalized body swelling
starting from legs and involving abdomen in 03 days.
He was being treated at home by a local health professional, Given 2 Liters of
Parenteral fluids daily for 03 days for a complaint of difficulty of taking oral meals.

6. Medical History…
Otherwise:
No abdominal pain, vomiting, diarrhea, constipation or yellowish eye discoloration.
No trauma hx, abnormal body movement, loss of consciousness or body weakness.
No reddish discoloration of urine, dysuria, urgency, frequency prior to obstructive symptoms
No bleeding sites, body rash or joint pain
No known chronic illness.
No Previous TB treatment or contact with TB patient
No history of smoking or alcohol intake.
No family history of bleeding disorder or similar illness.

7. Physical Examination
General Appearance : Acutely sick on Chronic basis.
Vital Sign: BP: 108/70 PR:112 RR: 20 T:36.70c SpO2: 97%,on ambient air
HEENT: Pale conjunctivae, Non-icteric sclera, Prominent Zygoma
LGS: No LAP, Thyroid not enlarged
CHEST: Decreased air entry on the lower 1/3 bilaterally with Coarse creps on post 1/3 chest.
CVS: Heart sounds (S1/S2) are well heard, no murmur or gallop.

8. Physical Examination…
Abdomen: Distended abdomen with slit umbilicus, soft, moves with respiration. No
Organomegally There is a 4*3 cm fungating mass at RLQ region, Suprapubic transverse surgical
scar from previous operation. Distended bladder.
GUS: No CVAT.
INT/MSS: Grade 3 Pedal/Pretibial/Sacral edema.
CNS: Conscious but disoriented, GCS 15/15
No cranial nerve deficit
Hypotonic Lower extremities with 0/4 Power.
Meningeal signs- absent

9. Cont..
Initial ASST:
◦ ?Pyonephrosis with Urosepsis
◦ AKI 20 to ?Septic ATN
◦ Anasarca 2o to ? Fluid Overload
◦ Uremic Encephalopathy
◦ SCC on Chemo radio Rx

10. Cont..
Plan:
CBC with Blood Group , OFT, Electrolytes, UAs, Occult Blood, Urine Culture, Blood
Culture, ESR, HBsAg, PICT.
◦ Abdominal U/s, CXR
◦ Catheter inserted drained 2 Liters of Turbid Urine.
◦ Ciprofloxacillin 400mg IV BID and Vancomycin 1gm IV BID initiated.
◦ PCM 1gm Po PRN

11. Investigations (02/02/2010)
11
CBC
WBC 8,500
Neut. 85.3 %
Lymph. 12.5 %
Hemoglobin 9.2 gm/dl
Hematocrit 27.2 %
Platelet 254,000
RFT
Cr 1.84 mg/dl
BUN 116 mg/dl
LFT
ALP 201.0 IU/L
GPT 24 IU/L
GOT 66 IU/L
BG & RH B+
HBsAg Neg.
PICT NR
Urinalysis
PH 6
Sp Gravity 1.02
Albumin +2
Blood +1
Leucocytes +2
Nitrite Neg.
Microscopy
Many Bacteria
Many Wbcs
Moderate Crystals [Ca Oxalate]

12. Investigations (03/02/2010)
Abdominal U/s:
• Liver has normal size, sharp edges and smooth contour, Normal homogenous echo pattern.
• Right kidney measures 9.7*4cm with Normal Corticomedullary Differentiation and cortical
echogenicity.
• Left Kidney measures 10.1*5.2 cm with dilated pelvis and calyces, with echo debris on dilated
pelvis.
• Index_ Left side minimal hydronephrosis with ?Pyonephrosis.

13. Emergency Resident Note [05/02/2010]
History: SAME + 2 weeks history of change in behavior where he talks irrelevant words and
subsequently became less communicable. For last 1 week prior to admission he had decrease in
urine amount, generalized body swelling starting from legs and involving the abdomen, LGIF,
Sweating, Loss of appetite
P/Ex: O - Acutely Sick Looking
◦ V/s: BP: 70/40 PR: 102 Weak RR: 20/min To: 36.4 Sao2: 91% with Atm Air
◦ GUS: UOP 500ml of clear concentrated urine/20hrs: no CVAT
◦ MSS: Left Inguinal healed scar/Right inguinal 4*2 cm fungating mass + HOMANS Sign –ve
◦ CNS: GCS [E4/V4/M5] 13/15

14. Cont..
REASST:
◦ SAME + Septic Shock with Urosepsis + Anasarca 20 to Severe Hypoalbuminemia.
Plan:
◦ Resuscitate with 500ml of NS fast then initiate Adrenaline Drip 50>>150 drops/min [2mg/500ml]
◦ Continue Ciprofloxacillin/Vancomycin + Ceftazidime with renal dose adjustment.
◦ GI Prophylaxis; NG tube feeding 300ml/4hrs ; RBS QID
◦ DVT Prophylaxis UFH 7,500 SC BID
◦ Consult Urology side and Renal side

15. Investigations (05/02/2010)
15
RFT
Cr 1.49 mg/dl
BUN 79.1 mg/dl
LFT
ALP 102.6 IU/L
GPT 14.3 IU/L
GOT 39.1 IU/L
Albumin 1.81gm/dl
DB 0.16
TB 0.1629
Serum Electrolytes
Na+ 138.2
K+ 3.94
Cl- 104.2
Total Ca+ 3.88
Serum
Phosphate
1.17

16. Ward Admission Note [06/02/10]
P: Same + Aspiration Pneumonia + ? Neurogenic Bladder + Chronic Left Leg DVT not on OAC [TASH
Historically]
S: Uncommunicative
O: G/A: ASL
◦ BP: 90/50 PR: 104 (Full) T: 37.7℃ Spo2: 93% with Atm air
Chest: Bilateral diffuse coarse Crepitations and transmitted sound
CNS: GCS [E3/V3/M5] 11/15 ; -ve Meningeal Signs
Plan :Continue resuscitation until BP>90/60 ; Added Metronidazole; NG tube Feeding planned but patient
refused and was put on Maintenance Fluid. CBC, CXR.

17. Investigations (06/02/2010)
18
CBC
WBC 6,000
Neut. 67.6 %
Lymph. 26 %
Mid 6.1%
Hemoglobin 6.9 gm/dl
Hematocrit 21.2 %
RBC 2.4*106
Platelet 186,000
RBC profile
MCV 88.3
MCH 28.8
MCHC 32.5
RDW 19.0

18. Investigations (08/02/2010)
Chest X-ray:
• Index_ Bilateral pericardial airspace
opacity 20 ? Aspiration Pneumonia

19. Investigations (08/02/2010)
20
CBC
WBC 3,600
Neut. 84.1 %
Lymph. 12 %
Mid 4.2%
Hemoglobin
5.0 gm/dl
27.2%
MCV/MCH/MCHC 89.3/26.9/30.1
RDW 18.2
*Platelet 37,000
MPV 7.8 fl
RFT
Cr 1.19 mg/dl
BUN 69.1 mg/dl
LFT
ALP 89.4 IU/L
GPT 13.2 IU/L
GOT 32.9 IU/L
RBS 121 mg/dl
Lipid Panel
Total Cholesterol 127.59
Triglyceride 164
HDL C 30.8
LDL C 54.12
Serum Electrolytes
Na+ 134
K+ 3.6
Cl- 110

20. Progress Note [08/02/2010]
P: Same + Clinically HIT Suspected [4T Score – 4]
S: NG Tube was not inserted b/c attendants refused.
O: G/A: ASL
◦ BP: 90/60 PR: 104 (Full) T: 37.7℃ Spo2: 93% with Atm air
Chest: Bilateral diffuse coarse Crepitations.
CNS: GCS [E3/V5/M6] 14/15 ; -ve Meningeal Signs
Plan : Stop DVT Prophylaxis; Monitor Platelets, Peripheral Morphology, Doppler U/s of Legs. Repeat CBC
with citrated tube. Consult Hematologist.

21. Investigations (12/02/2010)
22
CBC
WBC 8,300
Neut. 86.9 %
Lymph. 9 %
Mid 4.1%
Hemoglobin/HCT
8.5 gm/dl ;
24.4%
MCV/MCH/MCHC 90.7/31.6/34.8
RDW 19.8
*Platelet 193,000
RFT
Cr 1.06 mg/dl
BUN 70.5 mg/dl
LFT
ALP 92 IU/L
GPT 13.5 IU/L
GOT 36.7 IU/L
Serum Electrolytes
Na+ 142.8
K+ 4.25
Cl- 106.6
Peripheral Morphology
Normocytic Normochromic Cells
No platelet Clumping
No hyper segmented neutrophils or
blasts.

22. Investigations (12/02/2010)
Left Leg Doppler U/s:
• The common femoral veins are not completely compressible with anechoic content and have
no flow bilaterally.
• There is Significant subcutaneous edema of both Legs (More on the Left Leg).
• Impression_ Bilateral Acute DVT of the Common Femoral Veins.

23. Investigations (12/02/2010)
Coagulation Profile
[ICL]
PT 17.2 [10-14]
INR 1.27
PTT 23.8 [26.1-36.3]

24. Progress Note [12/02/2010]
P: SAME + Acute Bilateral common femoral vein DVT
S: Communicative
O: G/A: Lethargic
◦ BP: 90/60 PR: 100 (Full) RR: 26 T: 37.3℃ Spo2: 93% with Atm air
Chest: Bilateral diffuse fine Crepitations lower 1/3.
CNS: GCS [E3/V5/M6] 14/15 ; -ve Meningeal Signs
Plan : Initiate Anticoagulation Enoxaparin 60mg SC BID; Baseline Coagulation profile.

25. Progress Note [16/02/2010]
P: SAME + ? Massive PTE+ ?Septic Shock of Pulmonary Focus
S: Shortness of Breath with fast breathing and chest pain of 04hrs duration with palpitations.
O: G/A: ASL
◦ BP: 70/50 PR: 114 RR:32 T: 36.8℃ Spo2: 60-70% with Atm air; 92% with 15 Liters of Facemask O2
Chest: Bilateral diffuse coarse Crepitations and transmitted sound
CNS: GCS [E4/V4/M6] 14/15 ; -ve Meningeal Signs
A: Deteriorating
Plan : Initiate Dopamine Drip 10 ug/kg/min and escalate till 30ug/kg/min; Meropenem/Vancomycin started
Hydrocortisone 50mg QID Initiated ; 12 Lead ECG; Chest Ct Angiography; Communicate ICU for Transfer.

26. Pretest Probability of VTE [Wells Score]

27. Investigations (16/02/2010)
12 Lead ECG:
Impression
-Sinus Tachycardia [122]
-T wave Inversions on V2-V4

28. Progress Note [17/02/2010]
P: SAME + Impending T1 Respiratory failure 20 Massive PE
S: Fast Breathing
O: G/A: ASL
◦ BP: 80/50 PR: 104 RR:32 T: 37.7℃ Spo2: 83% with 15 L Of Facemask.
Chest: Bilateral diffuse coarse Crepitations and transmitted sound
CNS: GCS [E3/V5/M6] 14/15 ; -ve Meningeal Signs
A: Deteriorating
Plan : Continue resuscitation until BP>90/60

29. Death Circumstance [19/02/2010]
Despite max dose of Dopamine and epinephrine, BP was low and He became bradycardic.
CPR was tried *4 Cycles with 3 doses of Adrenalin
At 12:45 Am, Death Confirmed, he had no cardiac activity, Pupils dilated and Fixed.
Cause of Death:
◦ Cardiorespiratory Arrest 20 to Massive PE
◦ Refractory Septic Shock of Pulmonary Focus

30. Investigation Summary
CBC 02/02/10 06/02/10 08/02/10 12/02/10
WBC 8,500 6,000 2,600 8,300
Neut. 85.3% 67.6 % 84.1% 86.9%
Lymph. 12.5% 26 % 12% 9 %
Hemoglobin 9.2 g/dl 6.9 g/dl 5 g/dl 8.5 g/dl
Hematocrit 27.2 % 21.2 % 16.6% 24.4 %
MCV 88.3 89.3 90.7
MCH 28.8 26.9 31.6
RDW 19.8
Platelet 254,000 186,000 37,000 193,000
BG & RH B+
HBsAg Neg.
PICT NR
Urinalysis
PH 6
Sp Gravity 1.02
Albumin +2
Blood +1
Leucocytes +2
Nitrite Neg.
Microscopy
Many Bacteria
Many Wbcs
Moderate Crystals [Ca Oxalate]

31. Investigation Summary
Chemistry 12/01/10 02/02/10 05/02/10 08/02/10 12/02/2010
Cr 2.1 1.84 1.49 1.19 1.06
BUN 103 116 79.1 69.1 70.5
Na+ 138.2 142.8
K+ 3.94 4.25
Cl- 104.2 106.6
ALP 305 102.6 89.4 92
G0T 49 66 39.1 32.9 36.7
GPT 9 24 14.3 13.2 13.5
D- Bil 0.629
T- Bil 0.16
Albumin 1.81

32. Investigation Summary
• Doppler U/s: Impression_ Bilateral Acute DVT of the Common Femoral Veins.
• Echocardiography: Impression_Sinus Tachycardia [122] + T Wave Inversions on V2-V4
• CXR: Impression_ Bilateral pericardial airspace opacity 20 to ? Aspiration Pneumonia.

33. Vitals Summary

34. Questions/Comments???

35. Comments
Good Chart keeping
Adequate progress notes
Orders revised timely
V/s & Sao2 followed closely
Good antibiotic coverage
 Management Pitfalls
 Serial Monitoring Platelets; D dimer;
Antithrombin 3; Protein C; Fibrinogen
levels.
 Enoxaparin Initiation?
 Delayed Consideration of DVT?
 ICU Admission?
 Hematology Consultation?

36. THE PATIENT CASE
A 45 y/o M patient with Squamous Cell Cancer of the right inguinal region with vertebral bone
Metastasis on his 3rd Chemo [cisplatin/paclitaxel - Q21days] and Radiotherapy (palliative) @
TASH over the past year
Paraplegic patient 20 to Compressive Myelopathy 20 to Vertebral Metastasis 08 month.
Obstructive Uropathy 20 to ?Neurogenic Bladder with Urosepsis.
On UFH 7500 IU SC BID for 04 days; Platelets dropped from baseline 254,000>>>34,000.
Heparin stopped for 04 days Platelets recovered from 34,000>>193,000.
New onset Thrombosis diagnosed and started treatment with Enoxaparin.
Succumbed at 19/02/2010 with cause of death being CRA 20 to Massive PE + Refractory
Septic Shock.

37. Investigation Summary
254,000
186,000
34,000
193,000
08/02/2010
4th Day After
UFH Initiation
12/02/2010
5h Day After
UFH Stoppage
06/02/2010
1st Day After
UFH Initiation
• 12/02/2010
Doppler U/s: Impression_
Bilateral Acute DVT of the
Common Femoral Veins.

38. Discussion Point
Heparin Induced Thrombocytopenia and
Thrombosis [HITT]

39. Thrombocytopenia

40. Thrombocytopenia & Sepsis

43. Pathophysiology

46. HEP SCORE [HIT Expert Probability Score]
The HIT expert probability score (HEP) is a more detailed system developed
to improve on the diagnostic utility of the 4Ts score.
Testing in a validation cohort showed that the HEP model was 100% sensitive
and 60% specific for determining the presence of HIT at Cutoff of [2]
But at Cutoff of [5] 86% Sensitivity and 88% Specific , and demonstrated
better correlation with serologic HIT testing and better inter observer
agreement than the 4Ts score.
Nevertheless, the researchers cautioned that prospective multicenter
validation is warranted.
The Patient’s HEP SCORE = 5

47. Laboratory Tests

49. Management

50. Role of DOAC in HIT???

51. Role of DOAC in HIT???

53. Overtreatment of HIT

54. Take Home Message
Immediate discontinuation of ALL HEPARIN PRODUCTS in HIT
suspected cases.
Treating clotting with the Use of Alternative OAC (Novel Agents)
that are available in our setup like [Rivaroxaban].
More stringent probability testing like HEP in addition to 4T Score
to further Investigate or Change Anticoagulation.
Early suspicion of Thromboembolism in HIT Suspected cases.
Have a Flow Diagram for HIT Management in our Setup.

55. Choosing Wisely

56. Reference
Harrison’s Principles of Internal medicine 19th ed.
Up-to-date 21.6
Warkentin TE, Kelton JG. Interaction of Heparin with Platelets, Including Heparin-Induced
Thrombocytopenia. Bounameaux: Marcel Dekker, 1994:75±127.
University of Virginia Pharmacological Paper on HIT
Patient’s Chart