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Alan Chan, MD

Med-peds PGY4

“"Be obscure clearly."— E.B. White

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HPI: 21 yo previously healthy Caucausian male. Some bilateral flank discomfort for 1-2 days. This morning with some reddish urine that he thought was blood.

No dysuria. 2 wk ago with sore throat pain, mild neck ache, but afebrile. He was seen in the ER at that time and thought related to viral illness, but he received a course of amoxcillin. He recovered from that.

1 wk fatigue. He thought he saw some blood in his belly button as well earlier in the day.

Chief Complaint: flank pain and funny urine

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Medications• None – finished Amoxicillin

1 wk ago.

Allergies

NKDA

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PMH: as a child - meningitis

PSurgHx: none

ROS: No chills, fatigue, night sweats. No wt changes. No trauma, vision changes No rhinorrhea, sneezing; No dyspnea on exertion, edema, no shortness of breath, wheezeNo GI issues.

Some anterior tibial bruising he thinks is related to his “big dogs” getting rough.

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SH: Mr Goodcents manager. 1/2 ppd x ~ 3 yr. Occasional EtOH. Patient denies IVDU; occasional MJ and K2

FH: parents alive and healthy

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VS in ER: Temp 100.8, Resp 18, BP 142/88, Pulse 108. 99% on RA

General: Alert male appears stated age and in mild acute distress due back pain.

HEENT: EOMI, PERRL, pale conjunctiva. OP clear with intact dentition and 2 apparent caries, moist mucus membranes. Mild tonsillar erythema.

Gums appear reddish.

Neck: soft, supple, bilat swollen LAP < 1cm

Chest: CTA bilat, no wheezing

CVS: tachy regular rhythm S1, S2, no murmur

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Abd: BS +, non TTP. No guarding. Mild CVA tenderness

Ext: no edema, 2+ pulses

Neuro: CN 2-12 intact, no focal deficits. 5/5 strength with intact reflexes at knee, elbow. light touch intact

GU: no scrotal tenderness; Neg DRE.

Skin: a few areas of

pretibial

bruising and …

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Differential Diagnosis

CC: back pain

HPI: 21 yo with “red urine”, fatigue, reddish gums,

Recent dx of URI

PMH: none

Exam FindingsSeveral – flank pain, pale

conjunctiva, shotty LAP

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Laboratory Data

CBC

BMP

Urinalysis

Cardiac Enzymes

Liver Function Tests

Coagulation

Endocrinology

Serology

Other Serology

Cytology

Pathology

Microbiology

CXR

EKG

Ultrasound

CT Scan

Other Studies

Truman panel

Clinical Course

Differential Diagnosis

Discussion

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CBC

0.911.2

3011

Poly 22, B 6, L 57 M 15 %

MCV 91 (80-99)RDW 12 (<14.5)

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BMP

134

3.5

100

30

11

0.7104

AG 8 (3-15)

Ca 6.5 (8.8-10.5)Mg 1.5 (1.8-2.5)PO4 xx (2.4-4.7)

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Urine Analysis

Microscopic

5-10 wbc

TNTC rbc

5-10 Sq epi

2+ mucus

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Cardiac Enzymes

1st – TnI 0.01

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Liver Function Tests

AST 18 (15-41)

ALT 11 (7-35)

Alk Phos 41 (32-91)

Albumin 3.9 (3.5-4.8)

T Bilirubin 0.8 (0.3-1.2)

D Bilirubin xx (0.1-0.5)

Protein 7.7 (6.1-7.9)

Lipase 21 (18-51)

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Coagulation

PTT 32 (21-33)

PT 16 (10.3-13.0)

INR 1.54

Fibrinogen 115 (200-400

D-dimer 19 (0 to 0.50)

Retic 0.9

A-/-

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Endocrinology

TSH X (0.34-5.6)

Free T4 X (0.6-1.6)

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Serology

• HEPATITIS B SURFACE ANTIGEN Non-reactive• HEP B CORE ANTIBODY IGM Non-reactive• HEPATITIS A IGM Non-reactive• HEPATITIS C ANTIBODY nr

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Pathology

• Acute promyelocytic leukemia (M3).

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Other Serology

• Inflammatory markers – would have been very elevated

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Microbiology

• UCx neg

• BCx GPC in chains

Streptococcus dysgalactiae subsp equisimilis !! (pan sens)

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Chest X-ray

Lungs: The lung volumes are normal. No focal consolidation. Pulmonary vasculature is within normal limits.

Pleura: No pneumothorax. No pleural effusion.

Heart and Mediastinum: The cardiomediastinal silhouette is normal in size and contour. The great vessels are normal.

Osseous structures: Visualized osseous structures are intact.

IMPRESSION:

No acute cardiopulmonary process.

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EKG

• No EKG

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CT ABD/PELVIS – renal stone protocol

Findings:

Lung bases: No pleural effusion or consolidation. Heart is normal in size without pericardial effusion.

Abdomen: The noncontrasted liver, gallbladder, spleen, pancreas, and adrenal glands are normal. Renal contours are normal without evidence of hydronephrosis, perinephric fluid. A few scattered equivocal 1mm calcifications are suggested within each kidney. No intraperitoneal free air or fluid.

No mesenteric or retroperitoneal lymphadenopathy. Gastrointestinal tract is normal caliber without abnormal dilitation or thickening of bowel loops. The appendix is not identified.

Pelvis: Bladder is well distended without focal abnormalities. No pelvic mass, free fluid, or lymphadenopathy.

Bones and soft tissues: Skeletal structures are intact.

IMPRESSION

No evidence of obstructive uropathy. No acute abnormality detected.

Tiny, equivocal 1mm stones questioned within each kidney, nonobstructing.

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2-D Echocardiogram

CONCLUSIONS:

1. Mildly dilated left atrium by LA volume index calculation. 2. Overall left ventricular ejection fraction is estimated at 50%. 3. The left ventricular cavity size is mildly increased. 4. Mildly elevated pulmonary artery systolic pressure. 5. Normal LV diastolic function.

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Truman panel

• Not done!

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Clinical Course

• Pancytopenic, based on labs, clinical hx of bleeding, worried about acute leukemia.

• Also febrile, so cultures done and started on cefepime.

• Bone marrow aspiration done next morning.

• Acute promyleocyic leukemia most suspicious due to bleeding sites – was confirmed on pathology with (15;17)

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Discussion - Goals

• Overview of thrombocytopenia – in adults.

• Much more common in both inpatient and outpatient.

MKSAP Q?

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Thrombocytopenia (TCP) - definition

• platelet count < 150, 000. but 2.5% of the population has a count lower than this! • women have a slightly higher average

•Is it real??• EDTA induced clumping • of pregnancy, which can drop to 75-150K – typically

mild and asymptomatic, as long as no PMHx of TCP, late gestation, no fetal TCP, and resolved after delivery

• Wrong tube

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“minimal TCP”

• 100-150K in otherwise healthy adults• One long term study extrapolated data showing 10

years risk of persistent count <100K for ITP or other autoimmune dz as 6.9 and 12 %

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Thought process… destruction v production?

• Is it microangiopathic – having schistocytes, hemolytic anemia, with a high LDH? (nb. TCP and MAHA is all that is required to suspect TTP/HUS)

• OR

• Is it with underlying lymphoproliferative disease – Chronic lymphocytic leukemia, or Hodgkin’s

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More Destruction…

• Immune – ITP, TTP, sepsis like in the ICU setting, or severe infection. This results in autoimmune antiplatelet Ab– Can include drug related – see separate slide

• NOT immune – DIC, vasculitis, splenic sequestration

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Less production

• See blasts, leukoerythroblastic (teardrop, nucleated, or myeloid forms), oval macrocytic RBCs (with folate or B12 deficiency)

• 2 groups – acquired (marrow problem, drugs, infections – viral like

CMV, EBV, nutrition, aplastic, travel hx for malaria, the HIV.

– vs inherited. (Bernard Soulier syndrome, congenital problems – see other slide.)

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Ask…

• Chronic? Or new?– How many cell lines are affected?

• Are there other disease comorbidities?– Check a peripheral smear

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Bone marrow biopsy??

• Only do if unexplained TCP enough for a bleeding risk – OR

• Older than 60 years old with ITP to rule out those pesky myelodysplastic syndromes (MDS)

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Overview of those platelets.

• Daily production is 35-50K and survive 8-10 days• Typically 1/3 in the spleen

• To evaluate platelet function look at young platelets. Reticulated platelets is the young platelet fraction

• Can help differentiate between TCP with normal activity and increased turnover

• This test is at SLH. Uses a machine from Japan to test fluorescene intensity. Useful, but does not quite show normal distribution

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Drug induced

• Drug induced list at http://www.ouhsc.edu/platelets/• Huge list, but usually drug started in the past month.

• Usual suspects include heparin, sulfa drugs, quinine

drinks, ASA, and NSAIDs. • Cardiac meds like thiazides, some

antiarrhythmics• Valproic acid!

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HIT or Heparin Induced TCP

• 0.2 % to 5% of patients exposed to heparin over 4 days.

• Towards the lower end on unfractionated heparin; can have a delayed onset

• unknown incidence, but median about 14 days.

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Congenital problems

• May Hegglin – AD inheritance – giant platelets! Is a mutation of the myosin chain

• Alport – hematuria, renal failure, deafness, ocular like cataracts

• Bernard Soulier – AR inheritance, platelets are dysfunctional, bleeding due to no vWF receptors

• Wiskott Aldrich – X linked, triad of immunodefiency, eczema, and TCP with small platets

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Treatment

• Treat the underlying disorder!• > 10 K safe, unless Air Force or race car driver –

moderate TCP should restrict extreme activities• > 50 K – ok for most procedures, unless high risk for

bleeding• > 30-50 K for childbirth or dental extractions• If ITP – short 1 wk of steroids. If urgent surgery

required, then IVIG 0.4 to 1 gm/kg/day for 3 days or transfuse. (don’t have to treat kids typically)

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Question of the Day

• An asymptomatic 35 yo man comes for a routine annual. Medical and family histories are neg , takes a daily MVI

• Exam – afebrile , 120/70; 64/min, RR 14/min. There are no abnormal findings.

• Hgb 9, Leukocyte ct 2100, plt 135k, uric acid 11.6, LDH 890.

• PBS – blasts and promyelocytes. Cytogenetics t(15;17)• You start IVF and allopurinol, and then should?

• A Broad spectrum antibiotics• B Chemo• C chemo with all trans retinoic acid• D HLA typing

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• C – chemo and ATRA

• AML M3 type. 15; 17 translocation is a fusion gene PML/RARalpha. Response rate up to 95%

• Use chemo plus differentiating agent like ATRA or Arsenic trioxide.

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References

• MKSAP 14/15• Uptodate.com “Thrombocytopenia”. Accessed 4/20/2011.• Tefferi A., Hanson CA, Inwards DJ. How to Interpret and

Pursue an Abnormal Complete Blood Cell Count in Adults. Mayo Clinic Proc. 2005; 80(7):923-936.

• Abe Y, Wada H, Tomatsu H, et al. A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF). Thrombosis Research. 2006; 119, 463-469.

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