The purpose of this mini-series is to get in the mind of a treating physician when a patient such as this presents to the clinic or the ED in this case. The first part of this series is the introduction of the case with case history and initial lab testing. Please don’t hesitate to leave comments on what you think the diagnosis is and what other confirmatory tests need to be done if any as well as what treatment should consist of. This is mean’t to stimulate a discussion and there are no wrong answers. I am in no way a physician or at that level or have that education. I am a student with a passion for molecular diagnostics and creating these cases is a good way for me to practice real life scenarios through careful and diligent research as well as help others who think the same way. This case is no way real and all lab values are made up to the best of my knowledge. If anything is incorrect please do not hesitate to email me or leave a comment.
A 37-year-old South American male presented to his annual physical with his primary care physician with general fatigue, decreased appetite and weight loss over the past three weeks. The patient mentioned to his physician that he has had multiple nosebleeds throughout the last few weeks, an occurrence of multiple a week. The patients past medical history is unremarkable. No family history of bleeding tendencies. He is not taking any prescription medication and denies use of recreational drugs and only social use of alcohol. His physician ordered a CBC and a prothrombin time/activated partial thromboplastin time (PT/aPTT). Results are in table 1.
Two days later the patient presented to the emergency room with fever and heavy fatigue, he explained to the attending that it has been hard to do anything the last few days, and has been bed-ridden. Physical exam revealed bilateral bruising on the upper arms and forearms with purpura and petechiae. The attending physician ordered a full coagulation panel, platelet function tests (Ristocetin cofactor assay), bleeding time test for vWD, and full CBC with peripheral blood smear analysis. Results are summarized in table 2.
Later that evening the patient developed a high fever, and back/flank pain and was moved to the ICU. Blood cultures, CRP and a procalcitonin was ordered, results are in table 3.
Positive cultures for Staphylococcus aureus were found after 48-96 hours and the patient was started on a course of vancomycin and monitored closely.
Patient results indicated he was pancytopenic with a hemoglobin of 9.7 g/dL (Ref. 13.5-18.0 g/dL) and RBC count of 3.7×10^3/uL (Ref. 4.20-6.00×10^6 uL) with severe thrombocytopenia at 37×10^3/uL (Ref. 150-450×10^3/uL).
Initial coagulation results revealed significantly elevated PT and aPTT. The bleeding time test along with the results from the RCO indicate platelet dysfunction or acquired inhibition of platelets by accelerated destruction. Platelet aggregation studies were normal. RCO studies indicate factor VIII inhibition or consumption.
The peripheral blood smear confirmed leukopenia and thrombocytopenia and revealed abnormal promyelocytes with abundant azurophilic granulation and multiple auer rods in bundles. RBC morphology showed schistocytes and fragmented cells.
The attending followed up by ordering a complete fibrinogen, D-dimer and a plasminogen panel. Results are in table 4.
The significantly elevated D-dimer, elevation in t-PA and u-PA in combination with the significant decrease in fibrinogen, and plasminogen levels indicates primary hyperfibrinolysis.
The attending sent a blood sample to the Blood Bank laboratory and asked for units of packed red cells, platelets, and fresh frozen plasma (FFP) to be transfused. With the additional blood components, the patient was able to regain control over the thrombocytopenia, hemoglobin, fibrinogen and coagulation factor levels.
A bone marrow aspirate was ordered including cytology, cytochemistry, immunophenotyping, FISH (Fluorescence in situ hybridization), cytogenetics (chromosomal analysis and FISH) and RT-PCR for PML/RARA quantification of transcripts. The attending started the patient on all-trans retinoic acid (ATRA) as induction therapy.
FISH revealed the PML-RARA fusion gene present which was later quantified and confirmed by RT-PCR. PCR sequencing revealed a bcr-3 PML-breakpoint. Chromosomal analysis of the bone marrow identified a t(15;17) classic translocation. Cytochemistry revealed intensely positive reacting cells to myeloperoxidase and Sudan black B. Immunophenotyping results are in table 5.
RBC: 4.10×10^6/uL 4.20-6.00×10^6/uL
HGB: 12.9 g/dL 13.5-18.0 g/dL
HCT: 38.7% 40-54%
MCV: 88 fL 80-100 fL
MCH: 33.2 pg 26-34 pg
MCHC: 32.3 g/dL 32-36 g/dL
RDW: 13.5% 11.5-14.5%
RETIC: 0.8% 0.5-2.5%
NRBC: 0/100 WBC 0
WBC: 6.3×10^3/uL 3.6-10.6×10^3/uL
NEUT: 3.6×10^3/uL 1.7-7.5×10^3/uL
LYMPH: 1.9×10^3/uL 1.0-3.2×10^3/uL
MONO: 0.7×10^3/uL 0.1-1.3×10^3/uL
EO: 0.1×10^3/uL 0.0-0.3×10^3/uL
BASO: 0 0.0-0.2×10^3/uL
PLT: 111×10^3/uL 150-450×10^3/uL
MPV: 7.3 fL 7.0-12.0 fL
PT: 21 seconds 11-14 seconds
aPTT: 37 seconds 25-35 seconds
RBC: 3.7×10^3/uL 4.20-6.00×10^3/uL
HGB: 9.7 g/dL 13.5-18.0 g/dL
HCT: 28.9% 40-54%
MCV: 71 fL 80-100 fL
MCH: 31.8 pg 26-34 pg
MCHC: 33.1 g/dL 32-36 g/dL
RDW: 15.1% 11.5-14.5%
RETIC: 2.3% 0.5-2.5%
NRBC: 0/100 WBC 0
WBC: 2.5×10^3/uL 3.6-10.6×10^3/uL
NEUT: 1.3×10^3/uL 1.7-7.5×10^3/uL
LYMPH: 0.7×10^3/uL 1.0-3.2×10^3/uL
MONO: 0.3×10^3/uL 0.1-1.3×10^3/uL
EO: 0.1×10^3/uL 0.0-0.2×10^3/uL
BASO: 0.1×10^3/uL 0.0-0.3×10^3/uL
PLT: 37×10^3/uL 150-450×10^3/uL
MPV: 19.3 fL 7.0-12.0 fL
Myeloblasts: 7% 0%
Promyelocytes: 54% 0%
Myelocytes: 3% 0%
Metamyelocytes: 5% 0%
Bands: 0% 0%
PT: 33 seconds 11-14 seconds
aPTT: 63 seconds 25-35 seconds
BT: 13 minutes 1-9 minutes
RCO: 30% 50-150%
Platelet aggregation studies: Normal
Blood Cultures: POS Staph aureus NEG
Procalcitonin: 0.25 ng/mL <0.15 ng/mL
CRP: 23 mg/L 0-10 mg/L
Fibrinogen: 67 mg/dL
D-Dimer: >19,000 ng/mL