Can Iron Deficiency Cause Thrombocytopenia

1
Can Iron Deficiency Cause Thrombocytopenia?

• Grand Rounds
• David Tran
• 4/17/09

2
The Case

• CC A 49 yo African American woman with fatigue
• HPI
• A dentist without significant PMH. Not taking
  any medication.
• To ER with worsening fatigue, weakness, and
  lightheadedness for 2-3 days, but continued to
  work.
• On day of admission, too tired to work.
• Last 3 months menorrhagia (on/off for 2 weeks
  per menstrual cycle Irregular cycles lately).
  Very heavy last 4 days (1 pad/2hrs), clots.
• No other systemic symptoms (fever, night sweats,
  weight loss, swollen glands etc.)
• No history of excessive bleeding or easy
  brusiability.
• Never pregnant.
• No family history of bleeding or clotting
  problems.

3

• Physical exam
• All vital signs are within normal limits.
• The rest of exam was unremarkable except for very
  pale conjunctiva.
• Pelvic exam (per Gyn service) bleeding with
  large clots, otherwise unremarkable.

4
Labs

• WBC 4.7
• Hb 2.2
• Hct 7.5
• MCV 54.3
• Plt 23
• Retic 0.75

Ferritin lt4 Iron 158 TIBC 434 Transferrin sat
36 B12 560 RBC Folate 1561
TSH 2.77 ANA neg ESR 8 HIV neg
BMP normal. Cr 0.8 LFTs Normal Coagg
Normal Fibrinogen 227 Thrombin time 15.7
Retic 0.75 LDH 121 Haptoglobin 61.5 Coombs
negative
5
Imaging

• Abd/Pelvic US No hepatosplenomegaly. No uterine
  mass.
• Hysteroscopy no intrauterine mass.
• Smear RBC ghosts, profoundly
  microcytic/hypochromic. Low plts, no clumping,
  normal size. WBCs normal.

6

• Preliminary Diagnosis
• ITP exacerbating peri-menopausal bleeding
  leading to profound iron deficiency anemia.
• Treatment Prednisone, IVIG, Plt and pRBC
  transfusions
• Hospital course
• Hb/Hct increased appropriately with pRBCs.
• Platelet count did NOT respond to prednisone,
  IVIG and plt transfusion for several days.

7
Can iron deficiency, when this profound, cause
thrombocytopenia?

• Case reports in literature.
• Usually seen in cases of profound iron deficiency
  in children.
• Thrombocytopenia corrected rapidly with iron
  treatment.

8
A case series of 6 children
J Ped Hem/Onc, 2002, 24 (5) 380-384
9
All children were negative for Parvovirus. All
children received oral FeSO4 at 3-6mg elementary
iron per kg. Pts 2, 4, 5 , 6 got pRBCs. No other
treatments to raise plt counts
10

• An adult case report
• 30 yo multiparous AAF with mennorhagia.
• Hb 3, MCV 49, WBC 3.1, Plt 9k. Ferritin lt4.
• BM Biopsy Increased myeloiderythroid ratio,
  Decreased megakaryocytes/erythroid precursors.
  No stainable iron.
• FeSO4 300mg PO TID

Amer J Hem 24425-428 (1987)
Iron

• Repeat BM Bx on d18 Normal megakaryocyte
  number.

11

• Another adult case report
• 50 yo AAF with a bleeding intrauterine
  leiomyoma, otherwise healthy.
• Hb 1.6, MCV 67, Retic 1.8, Plt 23k, WBC 7.3,
  Ferritin 14.
• Received pRBC, Plts on d1, and FeSO4 325mg PO
  TID on day 2

• BM Bx on d10 (No BM before iron to compare)
  Increased megakaryocytes, erythroid hyperplasia.

Hosp Phys Aug 2001, 54, 49-51
12
A Mechanism?

• Thrombocytosis is common in mild-mod iron
  deficiency. Unclear pathophysiology. One
  hypothesis suggests the cross-reactivity of EPO
  with the TPO receptor.
• In severe iron deficiency, BM is exposed to
  chronically high EPO levels, favoring the
  erythroid lineage at the expense of plt
  production aka the stem cell competition
  hypothesis. (Blood 80(2)352-358, 1992)
• Iron plays a direct role in thrombopoiesis. The
  guinea pig phlebotomy experiment in the 1970s.
  (Amer J Med 57, 521-525, 1974). However, iron is
  NOT required for megakaryocyte development in
  humans.
• Perhaps, iron is important in megakaryocyte
  maturation and plt biogenesis or plt
  release/budding?

13
So what happened to our case patient?
IV Iron Dextran 1g
discharged
Hemoglobin (g/dl)
pRBCs
Days from Admission
14
1
2
0
0
1
0
0
0
SDP
8
0
0
6
0
0
IV Iron Dextran 1g
Platelet counts (x1000)
4
0
0
IVIG
IVIG
2
0
0
Discharged
0
0
1
2
3
4
5
8
1
5
Days from Admission
15
Conclusions

• Grade 3-4 thrombocytopenia can be associated with
  profound iron deficiency.
• Unclear mechanism
• Rapid recovery of plt counts has been reported
  upon iron treatment or repletion.