A challenging case scenario with Thrombocytopenia with VTE venous thromboembolism. How to diagnose thrombocytopenia? How to manage DVT and pulmonary embolism in thrombocytopenia? What is the threshold platelet count before surgery and intervention?

1. Thrombocytopenia with
VTE
Ahmed Yehia, MD
Under supervision of Prof. Hanan Taha
Immunology, Beni-Suef

5. Case
• A 40-year-old female underwent preoperative
assessment for cholecystectomy. Her CBC was as
follows.
• What’s the next step?
Hgb 12
PLT 120
WBC 8
Medicine &
Immunology

6. Pseudothrombocytopenia
•Analytical error (invitro).
PLTs aggregate in clumps, so counted as
WBCs by analyzers, which distinguish
between cells by their size, leading to
falsely low PLT count &
spuriously high WBCs.
First, exclude pseudothrombocytopenia.

7. platelet clumping

8. Platelet
Satellitis
m
NEJM

11. •PLT proved to be
120.
•The surgeon refused
to perform the
surgery.

12. • BMJ 2015;351:h5832 doi: 10.1136/bmj.h5832 (Published
18 November 2015)

13. Patients who are having invasive
procedures or surgery: Consider
prophylactic PLT transfusions to raise
the platelet count >
50×109/litre.
Consider a higher threshold (e.g. 50–75× 109 /l) for
patients at a high risk of bleeding after considering:
• the specific procedure
• the cause of the thrombocytopenia
• whether the patient’s PLT count is falling
• any coexisting causes of abnormal haemotasis.
100×109/l in patients having surgery in critical sites, such
as the CNS (including the posterior eye segment).

14. Offer prophylactic
PLT transfusions to
patients with a PLT
count < 10×109/L
who are not
bleeding or having
invasive procedures
or surgery, unless
there is an
alternative
treatment for the
condition or they
have a
contraindication to
PLT transfusion, e.g.:
Chronic bone marrow failure
Autoimmune thrombocytopenia
Heparin induced thrombocytopenia,
or
Thrombotic thrombocytopenic
purpura.

16. Finally….
cholecystectomy

18. All workup including
ANA was negative.
SO, primary ITP
(diagnosis of exclusion).

19. Follow up visit….
• CBC with differential is normal except for a low
platelet count of 50 x 109/L. She is asymptomatic
without any concerns for bleeding.
• How to treat?
A. Initiate low dose prednisone at 20mg/day for
‘mild ITP’
B. Discharge the patient back to her PCP for
annual lab work
C. Monitor her labs closely
D. Initiate dexamethasone at 40mg/day x 4 days
for a quick response

20. Recommendation
In adults with newly diagnosed ITP and a platelet count of ≥30 x
109/L who are asymptomatic or have minor mucocutaneous
bleeding, the panel recommends against corticosteroids rather
than management with observation (Strong recommendation based on
very low certainty in the evidence)
For patients with a platelet count at the lower end of this threshold, for those
with additional comorbidities that predispose to bleeding, anticoagulant or
antiplatelet medications, and upcoming procedures, and for elderly patients
(>60 years old), treatment with corticosteroids may be appropriate.

21. Recommendation
In adults with newly diagnosed ITP and a platelet count of <30 x 109/L who are
asymptomatic or have minor mucocutaneous bleeding, the panel suggests corticosteroids
rather than management with observation (Conditional recommendation based on very low
certainty in the evidence)
• The platelet count threshold at which bleeding risk increases and the natural
history of newly diagnosed ITP with a platelet count of <30 x109/l managed with
observation is not known.
• At higher platelet counts within this population or in younger patients,
observation may be reasonable.
• Consideration should be given to additional comorbidities, use of anticoagulants
or antiplatelet medications, need for upcoming procedures, and age of the
patient.

22. Case Continued:
• Her platelet count continues to be around 50 x 109/L on
monthly monitoring until 3 months later when she calls your
office because of ‘blood blisters’ appearing suddenly in her
mouth, large skin bruises on her arms and legs, and
menorrhagia.
• She also reports feeling more fatigued than usual.
• Her platelet count is 15 x 109/L and her hemoglobin has
dropped to 10 g/dL

23. How should you manage her severe ITP with bleeding?
A. Observation since she has an acute viral illness that will self resolve
B. Initiate low dose prednisone at 20mg/day and return to clinic in a week
C. Admit her to the hospital and start treatment with corticosteroids
D. Start eltrombopag for initial episode of symptomatic severe ITP

24. • In adults with newly diagnosed ITP and a platelet count of <20 x109/L who are
asymptomatic or have minor mucocutaneous bleeding, the panel suggests admission to
the hospital (Conditional recommendation based on very low certainty in the evidence)
• In adults with an established diagnosis of ITP and a platelet count of <20 x109/L who are
asymptomatic or have minor mucocutaneous bleeding, the panel suggests outpatient
management (Conditional recommendation based on very low certainty in the evidence)
• In adults with a platelet count of > 20 x109/L who are asymptomatic or have minor
mucocutaneous bleeding, the panel suggests outpatient management (Conditional
recommendation based on very low certainty in the evidence)
Three relevant recommendations:

25. Wet purpura: a sinister sign

26. Recommendation
In adults with newly diagnosed ITP, the panel recommends against a prolonged course (>6 weeks) of
prednisone rather than a short course (≤ 6 weeks) (Strong recommendation based on very low certainty in
the evidence)
• This represents a paradigmatic situation when a strong recommendation may be used despite
low confidence in the effects.
• There is no evidence for a benefit with longer duration of corticosteroids and high-quality
indirect evidence for adverse events with the use of courses of corticosteroids for > 6 weeks
based on.
• Side effects include hypertension, hyperglycemia, sleep and mood disturbances, gastric
irritation or ulcer formation, glaucoma, and osteoporosis.
• Corticosteroid course duration of 6 weeks represents a reasonable duration to provide a
standard maximum 21 days of treatment plus additional time for the taper.

27. Recommendation
In adults with newly diagnosed ITP requiring corticosteroids, the panel suggests either prednisone
(0.5 to 2.0 mg/kg/day) or dexamethasone (40 mg/day for 4 days) for initial therapy (Conditional
recommendation based on very low certainty in the evidence)
If rapidity of platelet count response is important, an initial
course of dexamethasone over prednisone may be preferred
given that dexamethasone showed increased desirable effects
with regards to response at 7 days.

28. Case, Continued:
• It has now been 6 months since you initiated corticosteroids for ITP.
• She has responded to prednisone but relapsed following a taper.
• She was subsequently treated with a course of dexamethasone, but invariably
relapsed again.
• She presents to your office to discuss options to prevent another relapse

29. Which of these statements is false about the next best course of action?
A. Rituximab has a durable effect on preventing ITP recurrences for 5 years in 75% with
relapsed ITP
B. Either thrombopoietin receptor agonist is an acceptable option for treatment of ITP
after failure of corticosteroid therapy
C. Splenectomy is effective for treatment of relapsed ITP, but carries increased risk of
long term infections and thrombosis
D. Several immunosuppressive agents like mycophenolate mofetil and azathioprine have
activity in adults with relapsed ITP, but are usually reserved for patients who fail
second- line therapies

30. Algorithm for the selection of
second-line therapy in adults
with ITP

31. Adult ITP Summary
Recommendation Population Intervention Comparator Strength
Certainty in the
evidence
1a
Newly Diagnosed
Platelet Count < 30 x 109/l
Asymptomatic or minor bleeding
Corticosteroids Observation Conditional Very low
1b
Newly Diagnosed
Platelet Count > 30 x 109/l
Asymptomatic or minor bleeding
Corticosteroids Observation Strong Very low
2a
Newly diagnosed
Platelet Count < 20 x 109/l
Asymptomatic or minor bleeding
Inpatient
(new patient)
Outpatient
(established
patient)
Conditional Very low
2b
Newly Diagnosed
Platelet Count > 20 x 109/l
Asymptomatic or minor bleeding
Inpatient Outpatient Conditional Very low

32. Adult ITP Summary
Recommendation Population Intervention Comparator Strength
Certainty in the
evidence
3
Newly diagnosed
Requiring
corticosteroids
Prolonged
corticosteroids
Short course of
corticosteroids
Strong Very low
4
Newly diagnosed
Requiring
corticosteroids
Prednisone Dexamethasone Conditional Very low
5 Newly diagnosed Corticosteroids
Corticosteroids plus
rituximab
Conditional Very low

33. 1 year later, she
developed these lesions.
ANA came positive,
1/160.
S. C3, C4, CBC are normal.
Anti-dsDNA is negative.

34. 2019 EULAR/ACR classification
criteria for SLE
• Criteria need not occur
simultaneously
• Within each domain, only
the highest-weighted
criterion is counted
toward the total score.

36. •So, we started on
hydroxychloroquine and
prednisolone for SLE.

37. Thrombocytopenia
(<100×109/L) has been
reported in 20% - 40% of
patients with SLE.
It may be the first
manifestation of lupus in
up to 16% of patients,
presenting months or as
early as 10 years before
diagnosis.
ITP SLE

38. • 3 months later, she presented with
severe acute dyspnea, hemoptysis.
SaO2
88
120 bpm

39. What is the best next step?
D-dimer then if elevated, CT pulmonary angiography and LL venous duplex.
Chest X-ray.
CT pulmonary angiography and LL venous duplex.
Salbutamol nebulizer.
Observation.

40. Pulmonary embolism risk scores
1.5
3
3
1
8.5
Wells
score

41. What is the best next step?
D-dimer then if elevated, CT pulmonary angiography and LL venous duplex.
Chest X-ray.
CT pulmonary angiography and LL venous duplex.
Salbutamol nebulizer.
Observation.

44. Hgb 10
PLT 33
WBCs 5

45. Myth:
Thrombosis
doesn’t occur in
thrombocytopenia.

46. What is the thrombocytopenia
D.D. in SLE??
SLE activity
Drugs: azathioprine,
MTX,
cyclophosphamide &
rarely
hydroxychloroquine
TMA
APS MAS
S.C3, C4,
anti-dsDNA,
ESR
Not
used No schistocytes
or hemolysis
No other
cytopenias,
Ferritin, TG, clinical
Clinical+
ACL , LAC DIC
Normal PT, PTT,
Fibrinogen,
No S or S of infection

47. D.D. of thrombosis
in our patient
(Thrombosis in
thrombocytopenia)
Drug induced: TPO RA, IVIG
Vaccine-induced Immune Thrombotic
Thrombocytopenia (VITT)
APS
SLE
Thrombotic microangiopathy TMA
Multifactorial

48. Vaccine-induced
Immune
Thrombotic
Thrombocytopenia
(VITT)
• Definitive Diagnosis (must meet
all five criteria):
1.COVID vaccine 4 to 42 days prior
to symptom onset#
2.Any venous or arterial thrombosis
(often cerebral or abdominal)
3.Thrombocytopenia (platelet count
< 150 x 109/L)*
4.Positive PF4 “HIT” (heparin-
induced thrombocytopenia) ELISA
5.Markedly elevated D-dimer (> 4
times upper limit of normal)

49. The difficult question: will
you anticoagulate with PLT
33.000/mm3?

50. Decisions in VTE with
thrombocytopenia
• Will you anticoagulate?
• If yes, what is the dose?
• If no, what is the alternatives?

51. Bleeding
Thrombosis

52. • There is no simple
formula for calculating
which risk (thrombosis
or bleeding) is greater.
• There is no
anticoagulant that can
reduce thrombotic risk
without also increasing
bleeding risk.

53. 2019 update of the
EULAR
recommendations
for the
management of
SLE
First-line treatment of significant lupus
thrombocytopenia (PLT count < 30 000/mm3)
consists of moderate/high doses of GC in
combination with IS (AZA, MMF or
cyclosporine; the latter having the least potential
for myelotoxicity) to facilitate GC-sparing.
Initial therapy with pulses of intravenous MP
(1–3 days) is encouraged.
IVIG may be considered in the acute phase, in
cases of inadequate response to high-dose GC
or to avoid GC-related infectious
complications.

54. 2019 update of the
EULAR
recommendations for
the management of
SLE
Treatment of thrombocytopenia is typically lengthy
& often characterized by relapses during GC
tapering.
In patients with no response to GC (ie, failure to
reach a platelet count >50 000/mm3) or relapses,
RTX should be considered, considering also its
efficacy in ITP.
CYC may also be considered in such cases.
Thrombopoietin agonists or splenectomy should be
reserved as last options.

55. Oncologist

56. Anticoagulation for
individuals with
cancer and
thrombocytopenia
who develop venous
thromboembolism

59. • PLT 5 days later became 74.000/mm3.
• On day 9, she developed progressive skin necrosis at one of the
enoxaparin injection sites. PLT became 28.000/mm3.

60. Myth: HIT occurs only
with unfractionated
heparin.

63. Having SLE and APS
then developing HIT, we
stopped LMWH and we
had to give rivaroxaban.
She is now stable with
improvement of skin
lesions and stable PLT
count > 100.000/mm3.

64. PLT--
aPL
Thrombocytopenia is currently considered as a “non
criteria” manifestation for APS diagnosis.

65. ITP APS

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