ZSFG AM Report Pearls 3/1/18: Ain’t No Platelet High Enough: Thrombocytosis DDx, Complications, and Treatment

Thank you to the ZSFG team for presenting a great case of a patient with a gluteal abscess who presented with a significant neutrophilic leukocytosis and extreme thrombocytosis. We reviewed the differential, complications, and treatment of thrombocytosis.


Pearls on Etiology:
  • Degree of elevation does not help distinguish reactive (aka seconday) thrombocytosis from primary thrombocytosis
    • One study demonstrated that 82% of pts with plts >1 million were reactive
  • There are presently no diagnostic findings that can definitively distinguish between clonal and secondary (reactive) thrombocytosis.
Differential Diagnosis for Thrombocytosis:
  • Reactive Thrombocytosis (Secondary)
    • Most common
    • Secondary process from surgery, infection, cancer, chronic inflammation
    • Note that occult malignancy could cause this and is difficult to diagnose
  • Familial Thrombocytosis (Familial/Congenital)
    • Rare cases of autosomal dominant disorder, gain of function mutations in thrombopoietin gene
    • However, now recognized as a genetically heterogeneous disorder
  • Clonal Thrombocytosis (Primary)
    • Chronic myeloproliferative disorder
      • Essential thrombocytosis
      • Polycythemia vera
      • May occur in other myeloproliferative disorder but ET and PV are most common (for example, prefibrotic myelofibrosis which can evolve into overt myelofibrosis)
Clinical Complications from Thrombocytosis:
Clonal Thrombocytosis
Secondary (Reactive) Thrombocytosis
Underlying systemic disease
Often clinically apparent
Digital or cerebrovascular ischemia
Large vessel arterial or venous thrombosis
Increased risk
Bleeding complications
Increased risk
Yes, in about 40% of pts
Peripheral blood smear
Giant platelets
Normal platelets
Platelet function
May be abnormal
Bone marrow megakarylocytes (Number)
Morphologic Features
Giant, dysplastic forms w/ increased ploidy, assoc w/ large masses of platelet debrid
Treatment Algorithm:



Source: Schafer, AI. (2004). Thrombocytosis. NEJM. 350:1211-9.

Evernote: https://www.evernote.com/shard/s509/sh/5fd9cf19-9708-443f-b65c-fc0400c5c298/683c51013b18898fc7554eb5694aca17

VA Morning Report 3.6.18: Sailors’ malady

Case summary: Thanks to Arvind for presenting the fascinating case of a 72F with remote PMH of breast cancer s/p lumpectomy, lymph node dissection and XRT, who presented with 2-3 weeks of progressive DOE, anemia/thrombocytopenia, AKI and rash. Although there was initial concern for vasculitis, a dietary review by Nutrition led to the correct diagnosis: scurvy (severe vitamin C deficiency)!


1. Before bee-lining for a Rheum consult, recall the specific dermatologic manifestations of vasculitis: palpable purpura, petechiae, vesicles, pustules, urticaria, & splinter hemorrhages, livedo reticularis, subcutaneous nodules, ulcers, digital infarcts, and papulonecrotic lesions. Biopsy should show cellular infiltrates and fibrinoid necrosis within and around the vessel wall, referred to as leukocytoclastic vasculitis.

2. This patient got a CT chest/abdomen/pelvis to look for recurrence of her breast cancer. We reviewed that although these imaging modalities are great for picking up metastatic disease, they may miss locoregional recurrence, which accounts for 15 to 40% of recurrences, or contralateral breast cancer. The test of choice for evaluation of locoregional recurrence is 1) diagnostic mammography, 2) breast MRI if mammography is inconclusive.

3. Think about scurvy in patients who are institutionalized, have restricted diets or poor food access and present with 1) neurologic symptoms (lethargy, arthralgias, irritability), 2) dermatologic manifestations (especially easy bruising, gingival hemorrhage, poor wound healing) and 3) anemia (seen in 75% of patients).

Cutaneous manifestations of vasculitis

  • This patient’s multi-system findings– particularly skin rash and AKI with hematuria–initially raised concern for vasculitis. Goop reminded us of the specific dermatologic findings of vasculitis.
  • On biopsy: “leukocytoclastic vascultis,” which is characterized by cellular infiltrates and fibrinoid necrosis within and around the vessel wall.
  • Small vessel (Henoch–Schönlein purpura, urticarial vasculitis, cryoglobulinemic vasculitis, and cutaneous small-vessel vasculitis)
    • Palpable purpura is the hallmark
    • Other findings: Petechiae, vesicles, pustules, urticaria, & splinter hemorrhages
  • Medium vessel (PAN and Kawasaki disease)
    • Livedo reticularis, subcutaneous nodules, ulcers, digital infarcts, and papulonecrotic lesions
  • Mixed-vessel vasculitis (microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (eGPA), and granulomatosis with polyangiitis (GPA)
    • Combination of small/medium vessel skin findings
  • Large vessel (Takayasu arteritis or giant-cell (temporal) arteritis)
    • Typically no skin findings
    • Nondermatologic findings such as limb or jaw claudication, bruits, pulse defects, and new onset of headache.


Reference: Xu et al. Cutaneous Manifestations of Vasculitis. Semin Arthritis Rheum. 2009 Apr;38(5):348-60.

Scurvy 101

  • Historical interlude:
    • Between 1500 and 1800 BC, scurvy killed more sailors than all other diseases and disasters combined.
    • In 1747, Scottish surgeon James Lind conducted what is considered to be the first controlled trial in medicine and determined that citrus fruits were curative of the disease
    • Daily provision of lemon juice to sailors on long voyages was not implemented until the late 18th century.
    • Scurvy was effectively eradicated at sea but reemerged among the pediatric population during the 19th century, when heated milk and processed foods became staples in the diet of infants.
    • Now, this diagnosis is infrequently encountered in industrialized nations, and diagnosis is often delayed. Think about it in:
      • those with poor nutrition or extreme dietary restrictions (including picky toddlers!)
      • the isolated elderly
      • the institutionalized.
  • Vitamin C is required for biosynthesis and hydroxylation of hormones, neurotransmitters, and mature collagen–> prominent clinical features:
    • Generalized symptoms- fatigue, myalgias, arthralgias, weakness, anorexia, weight loss, and irritability.

    • Dermatologic manifestations- follicular hyperkeratosis with perifollicular hemorrhage surrounding twisted, brittle hairs (corkscrew hairs), ecchymoses, poor wound healing, and swelling in the legs.

    • Gingival swelling and hemorrhage

    • Soft-tissue or subperiosteal hemorrhage, most commonly affecting the legs, may cause pain so severe that affected persons are unwilling to walk.

    • Anemia occurs in 75% of patients with scurvy and is the only routine laboratory abnormality. Mechanisms: blood loss into tissues or from the gastrointestinal tract, intravascular hemolysis, and coexisting folate and iron deficiencies.

    • Left untreated, scurvy may result in cardiorespiratory failure and death, the mechanisms of which are incompletely understood.
  • Diagnosis and treatment:
    • Test early! Levels will rapidly normalize, so false negatives can occur if a patient is tested after he/she starts eating vitamin C as part of a hospital diet!
    • Treatment is with high-dose vitamin C, and symptoms should improve within days to weeks.

Reference: a great NEJM case with a review of scurvy! Hafez, D. et al. A Deficient Diagnosis. N Engl J Med 2016; 374:1369-1374

Moffitt Cardiology Report – 3.6.18 – Syncope

Thank you to Armond for presenting a case of a elderly man with AF and Parkinson disease presenting with exertional syncope found to have a depressed EF and cath showing 95% LAD occlusion.

Key Pearls

  1. When working up a patient who presents with syncope the history is the most important diagnostic tool.
  2. Concerning features suggestive of cardiac cause include syncope with exertion, lack of prodromal symptoms, and trauma.
  3. After syncope from ANY cause you may see myoclonic jerks 2/2 to global anoxia of the brain. See this video for an example of healthy medical students with induced syncope and subsequent myoclonic jerks.   https://youtube.com/watch?v=YaktxCXiUyY
  4. We define Ventricular Tachycardia as > or = 3 VPCs at rate of at least 100. Sustained VT is > 30 seconds or VT with hemodynamic compromise. Non-sustained VT is < 30 seconds.

General Approach to Syncope

  • Cardiac
    • Structural: chest pain, dyspnea, exertional, post-operative
    • Arrhythmia: sudden syncope, injury, palpitations
  • Reflex Mediated
    • Vasovagal: warmth, nausea, prodrome, tunnel vision
    • Situational: occurs after certain activity (micturition, cough)
    • Neurocardiogenic: Provocable stimulus
    • Carotid sinus hypersensitivity
  • Neurologic
    • Seizures
  • Orthostatic Hypotension
  • Medications
  • Unknown

Clinical Features Suggestive of VT

    • Age > 35 (positive predictive value of 85%)
    • Structural heart disease!!
    • Previous MI or hx of ischemic heart disease
    • Congestive heart failure
    • Cardiomyopathy
    • Family history of sudden cardiac death (suggesting conditions such as HOCM, congenital long QT syndrome, Brugada syndrome or arrhythmogenic right ventricular dysplasia that are associated with episodes of VT)
  • WHEN is doubt shock it out!!



Thank you to Michelle Mourad for this educational slide from last week’s awesome M@M.

Syncope Evernote: https://www.evernote.com/shard/s462/sh/9c271d40-2562-48c1-9bd1-cb6f54179d73/33f49d97647c6e61252807c98013e7dd