DRUG-INDUCED IMMUNE THROMBOCYTOPENIA

Dr. Jensen presented a great case of thrombocytopenia at noon report today. An older gentleman with recent STEMI s/p PCI with DES presented with profound thrombocytopenia (platelets 14 —> 1) and was ultimately diagnosed with drug-induced immune thrombocytopenia due to Tirofiban (received at time of PCI). The diagnosis was confirmed with drug-dependent platelet antibody testing. Treatment was challenging given his recent STEMI with DES, concern for risk of myocardial wall rupture with high-dose steroids, and onset of GI bleeding. He was thus treated with the “platelet boiler-maker”.

Platelet Boilermaker…

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What’s that? A 24-hour continuous infusion of IVIG,1 g/kg, and four units of apheresis platelets, each infused over 6 h.

When do I use it? With major hemorrhage or need for rapid hemostasis in patients with ITP

Does it work? In a retrospective review at OHSU (by our very own heme team), 65% of patients showed a response after 24 hours (defined as platelets >30,000/uL and a twofold increase in baseline levels) .

Biotin! Wreaking Havoc on your endocrinology lab interpretation!

As our patient's medication list become longer and longer with supplements, let's take a moment to talk about biotin.

BIOTIN!

The B vitamin that is marketed to improve hair and nail health can make a mess of your endocrinology labs. Dr. Hayward brought this up at her noon report on Monday on oligomenorrhea and this was discussed in the last year at our DOM Grand Rounds.

What's so confusing about biotin and how it affects your labs, is it can cause both positive and negative interference on assays. It can also cause false positive for TPO antibodies despite a patient having no phenotypic evidence of Grave's disease.

 
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When in doubt, talk with the lab and/or endocrinology to help with testing. Endocrinology recommends holding biotin for at least 4 weeks before retesting.

Oligomenorrhea in the clinic!

Dr. Lesleann Hayward presented a fascinating case from clinic. A woman in her 40s presented with oligomenorrhea x4 years without weight loss, excessive exercise, galactorrhea, hirsutism, or menopausal sx. BMI, TSH, prolactin were normal. FSH was inappropriately normal with a very elevated estrogen level (like 2000s). Transvaginal US surprisingly didn't show any endometrial thickening but noted numerous ovarian cysts. Testosterone level was normal suggesting against PCOS. The patient's estrogen level continued to rise but normalized after stopping her biotin supplement and starting on low-dose OCPs. Though this case still leaves us puzzled, it was a great refresher on how to work up amenorrhea and oligomenorrhea in the clinic. When in doubt, no one will fault you for involving gynecology or endocrinology.

Let's refresh with some definitions:

Amenorrhea: lack of menses.

  • primary: lack of menses by age 15 or age 13 is no breast development (usually an anatomic, genetic, or hormone deficiency an d not discussed here as not typically seen in adult world). If uterus is absent, get a karyotype to evaluate for Turners.
  • secondary: absence of menses for >3 months in women who previously had a regular menstrual cycles OR absence of menses for > 6 months in woman with previously irregular menstrual cycles.

Oligomenorrhea: fewer than nine menstrual cycles per year or cycle length greater than 35 day


In thinking of possible pathology, it can be helpful to think of the hypopituitary axis and what can go wrong at each level.

 
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However a more practical approach is to get standard amenorrhea labs and work through this algorithm for cause. (fun exercise to test your understanding of the hypothalamic-pituitary-ovarian axis!)

Let's order some labs:

The initial labs for someone with amenorrhea or oligomenorrhea is a beta-HCG (VERY important), prolactin, TSH, FSH, LH, estrogen (+ testosterone if hirsutism). Remember, low BMI, excessive exercise, and eating disorders can also cause amenorrhea so get a thorough history.

Read our next blog   on the pains of biotin supplementation on hormone lab assays which was felt to be a confounder in this case.    A progesterone challenge can be considered to see if someone is progesterone deficient (will bleed within 5 days of giving progesterone). This suggests eugonadotrophic amenorrhea and should raise concern for structural abnormalities and suggests the patient is making estrogen but is anovulatory.    Resources:   UpToDate:  Welt and Barbieri. “ Evaluation and management of secondary amenorrhea.” UpToDate. 5/2018.    AAFP:  Klein, et al. “Amenorrhea: A Systematic Approach to Diagnosis and Management.” AAFP. 7/2019.  https://www.aafp.org/afp/2019/0701/p39.html

Read our next blog on the pains of biotin supplementation on hormone lab assays which was felt to be a confounder in this case.

A progesterone challenge can be considered to see if someone is progesterone deficient (will bleed within 5 days of giving progesterone). This suggests eugonadotrophic amenorrhea and should raise concern for structural abnormalities and suggests the patient is making estrogen but is anovulatory.

Resources:

UpToDate: Welt and Barbieri. “Evaluation and management of secondary amenorrhea.” UpToDate. 5/2018.

AAFP: Klein, et al. “Amenorrhea: A Systematic Approach to Diagnosis and Management.” AAFP. 7/2019. https://www.aafp.org/afp/2019/0701/p39.html

African Tick Bite Fever

Dr. Westwood presented a great case of a patient who had just returned from traveling on Safari to Sub-Saharan Africa who presented with acute fevers, chills, drenching night sweats and an exquisitely painful erythematous/violacious left first metatarsal rash. He was initially admitted to the vascular surgery service and underwent CTA of the lower extremity and TTE without evidence of thrombus and was started on cefazolin and a heparin drip. Over the course of the next coming days, his cellulitis quickly spread more proximally and he was started on vancomycin and piperacillin tazobactam. Unfortunately, despite broad spectrum antibiotics, the erythema continued to spread and inflammatory markers continued to rise. General surgery had also evaluated the patient and did not feel like he warranted a surgical intervention?

What’s your summary statement and what’s your differential for a worsening cellulitis despite broad spectrum antibiotics?

We don’t see these types of things very often. Here’s a resource to help us form our differential

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ID and dermatology was consulted. ID recommended starting the patient on doxycycline for atypical coverage. A skin biopsy revealed: neutrophilic dermatitis with vascultitis + papillary edema with ? ecthyma, negative for bacterial/fungal/AFB. After addition of doxycycline, his rash started to regress. 2 weeks later, a broad range PCR returned positive for Rickettsia Africae

Polycythemia

Dr. Lindquist presented a case of a patient who presented with chronic/progressive abdominal pain who was found to have an H/H of 23/68! (comment below with the highest H/H you’ve ever seen!). He was found to have a splenic vein thrombosis on CT abd & pelvis.

Approach to polycythemia:

After confirming the labs are correct and considering potential secondary causes of polycythemia, initial work up includes getting a JAK2 mutation and EPO level.

Dr. Lindquist created a nice schema for thinking about polycythemia based on presence of HIGH or LOW EPO.

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This patient ended up having a positive JAK2 and low EPO level and was diagnosed with Polycythemia Vera. In order to diagnose someone with Polycythemia Vera, you need to meet either all WHO 3 major criteria or 2 major + 1 minor criteria:

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Please see this great, new review and update on the treatment of polycythemia vera for more details (Polycythemia Vera and Essential Thrombocytopenia: 2019 update on diagnosis, risk stratification and management. Tefferi and Barbui. AJH 2019) but here is a brief overview of treatment:

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Weight loss

Dr. Gretl Lam recently presented a case of a 19-year-old obese male seen in primary care clinic for 80 lb unintentional weight loss. Drs. Kaleb Keyserling and Emily Watkins from the VA primary care clinic were present for this report and provided valuable outpatient perspective in the assessment and management of this patient.

We began by creating a framework for unintentional weight loss, to help target our history, exam and diagnostic work up, while keeping pretest probabilities in mind.

Unintentional Weight loss: A framework

Malignancy: lymphoma and testicular cancer being most likely in the age cohort

GI Disorders: PUD, Malabsorptive processes (Celiac), Inflammatory Bowel Disease

Endocrinopathies: Diabetes Mellitus, Hyperthyroidism, Adrenal Insufficiency

Infectious Diseases: HIV, TB (though less likely in the absence of risk factors)

Chronic Disease: Lung, Liver, Kidney

Neurologic Diseases

Rheumatologic Diseases

Psychiatric Illnesses: Depression, Anxiety, Eating Disorder

Medication/Substance Use

Given the patient’s age and lack of prior medical history the residents felt psychiatric illness and or substance use disorder was high on the differential.

Back to our case

On interview, the patient endorsed excess thirst, polydipsia and polyuria. He denied substance use or mood disorder, though history was obtained in the presence of his mother. Physical exam was grossly normal. Given this history, an endocrinopathy, particularly new onset diabetes was felt to be high on the differential. CBC, CMP, UA, Hemaglobin A1c and TSH were checked, which were grossly normal with the exception of Hemaglobin A1c of 12.7.

The patient was started on insulin while workup for auto-antibodies (GAD 65) was initiated to help differentiate between type 1 and type 2 diabetes. This work up was negative. Insulin was subsequently discontinued for metformin, with thought that this case of undifferentiated diabetes was most likely early onset type 2 diabetes.

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Dr. Emily Watkins’ Pearls

1) Every teenage patient, part of the encounter should be conducted in the absence of the parent. Dr. Watson shared that she would set this expectation with every teenage patient and their parent and in doing so would normalize the situation. Meaningful discussions regarding substance use and sexual habits will most often only be obtained when a parent is out of the room.

2) Eating disorders can be difficult to broach with teenage patients. Dr. Watson’s practice is to initiate the conversation by asking “how do you feel about your body?”

3) Any patient with family history of autoimmune disorder should be screened for diabetes, thyroid disorder and celiac disease at the same time.

4) A patient with a new diagnosis of diabetes in the outpatient setting, can be managed outpatient if clinically stable and good access to care/ability to follow-up.









Liver Abscess

Dr. Johnny Cai presented a case of a woman with a history of a pancreatic tail cyst who had two weeks of progressive RUQ pain, fever, and night sweats. She was hemodynamically stable, but her labs revealed a hepatocellular liver injury and a severe leukocytosis. RUQ ultrasound revealed pneumobilia without common bile duct dilatation, cholelithiasis or pericholecystic fluid.

Pneumobilia, you say?

The differential for pneumobilia is short -- post-procedural vs BADNESS (like gas-producing bacterial infection).

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The team then proceeded with a CT (shown here):

“gas and fluid filled structure 5x4 cm in segment 4 of the liver consistent with abscess without clear source.”

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When thinking about a liver abscess, it can be helpful to try to classify it further into pyogenic (most common) vs less common causes such as amebic or unusual infections (TB, Echinococcus, candidal). Your history should alert you if you should be thinking about atypical liver abscesses. Echinococcus has a very distinct look on imaging and should not be aspirated for culture as this can be lethal.

You should also ensure you get blood cultures as liver abscesses can form from hematogenous spread.

A liver abscess?

The patient was started on pipercillin/tazobactam and IR aspirated the liver abscess and placed a drain. The aspirate culture never grew anything (suspected sterilized with antibiotics).

Her leukocytosis was not improving and thus she was -reimaged without change in abscess and had another drain placed. THIS IS A GOOD TEACHING POINT: if the clinical picture isn’t improving, make sure you truly have source control (drain not in right place, another process going on, wrong antibiotics, etc.) After her clinical picture started to improve, she was transitioned to metronidazole and moxifloxacin to complete a 6 week course.

References:

  • UptoDate “Pyogenic Liver Abscess”

  • Lübbert C, Wiegand J, Karlas T. Therapy of Liver Abscesses. Viszeralmedizin. 2014;30(5):334–341

  • Rathimian, J et al. Clinical Infectious Diseases. 2004 Dec 1;39(11):1654-9

  • Tan YM, Chung AY, Chow PK, et al. Ann Surg. 2005;241(3):485–490

  • Wong, Wai Man et al. Journal of Gastroenterology and Hepatology. (2002) 17, 1001–1007