Some common physical exam findings of liver disease:

• Fetor hepaticus (breath smells like a freshly opened corpse)
• Spider nevi
• Gynecomastia
• Jaundice / Scleral icterus
• Ascites
• Caput medusae (dilated abdominal veins)
• Rectal varices
• Testicular atrophy
• Palmar erythema
• Dupuytren’s contracture

MELD Score:

• Predicts 3-month survival in patients with cirrhosis.  In cirrhotic patients, an increasing MELD is associated with increasing severity of hepatic dysfunction and increased 3-month mortality.

Factors that go into MELD: serum bilirubin, serum creatinine, INR, sodium (added 1/2016), +/- hemodialysis > 2 in the past week

MELD Interpretation:

Maddrey Discriminant Function:

DF = (4.6 x [prothrombin time] – [control prothrombin time]) + (serum bilirubin)

• DF > 32 indicates SEVERE alcoholic hepatitis
• High short term mortality (20-30% within 1 month; 30-40% within 6 months)
• Patient may benefit from glucocorticoids
• Prednisone requires hepatic conversion to the active form (prednisolone)
• Multiple trials have showed a reduced short term mortality in patients with a DF >32 (NNT 3-68); no effect in patients <32

STOPAH Trial:

• Multicenter, double blinded, RTC
• 1103 patients with DF >32 and TBili > 4.7
• 4 treatment groups: (placebo, pentoxifylline + placebo, prednisolone + placebo, pentoxifylline + prednisolone)
• Prednisolone had a significant 28 day mortality benefit (after adjusting factors), but the benefit was lost at 90 days and 1 year
• Pentoxifylline did not improve survival compared to placebo

  

Hepatorenal Syndrome:

Characteristics of HRS:

• Clinically evidence acute or chronic liver disease
• Progressive rise in serum creatinine
• Normal urine sediment
• Absent/Minimal proteinuria
• Low urine sodium (often < 10 mEq/L)
• Oliguria

Types of HRS:

Type 1: more serious; at least a 2 fold increase in serum creatinine to >2.5 mg/dL in less than 2 weeks

Type 2: less severe; major clinical feature is ascites resistant to diuretics

Etiology:

• Splanchnic vasodilation ⇒ reduced effective circulating volume ⇒ renal failure
• MAP = CO x SVR; In patients with HRS, SVR is decreased (from splanchnic vasodilation); hence treatment is aimed at improving SVR and MAP.

Diagnosis of HRS is one of exclusion:

• Normal urinary sediment
• Absence of nephrotoxic meds
• No hypotension
• Urine studies similar to pre-renal AKI

Fluid challenge with albumin: 1 g/kg albumin (max 100 g) daily for 2 days

• If renal function IMPROVES, suggestive of pre-renal AKI
• If renal function continues to DECLINES, suggestive of HRS

Treatment of HRS:

• Liver transplantation – TREATMENT OF CHOICE
• Medical Management:
  • ICU: treat with norepinephrine and albumin
  • Non-ICU: treat with midodrine, octreotide, and albumin

Peritoneal Fluid Analysis:

• Increased accumulation:
  • Increased capillary permeability
  • Increased venous pressure
  • Decreased protein (oncotic pressure)
• Decreased clearance:
  • Increased lymphatic obstruction

Causes of ascities:

Transudative (<30 g/L ~ systemic disease)

• Liver (cirrhosis)
• Cardiac (RHF, constrictive pericarditis, etc.)
• Renal failure
• Hypoalbuminemia (nephrotic syndrome)

Exudative (>30 g/L ~ local disease)

• Malignancy
• Venous obstruction (Budd-Chiari)
• Pancreatitis
• Lymph obstruction
• Infection (especially TB)

SBP:

1. PMNs > 250 cells/mm3
2. + bacterial culture
3. Absence of secondary causes (i.e. bowel perforation, abscess, etc.)

SAAG:

• >1.1 g/dL ~ portal hypertension (97% accurate) => Transudative effusion
• <1.1 g/dL ~ absence of portal hypertension => Exudative effusion

Lymphocytic Ascities:

• Peritoneal carcinomatosis (>50% lymphocytes)
• Peritoneal TB (>70% lymphocytes)

Sister Mary Joseph’s Sign: hard periumbilica nodule ~ indicative of metastatic disease to abdomen – usually pelvic/GI primary.

Virchow’s Node: enlarged lymph node in the left supraclavicular fossa ~ indicates cancer in the abdomen.

Remember the 3 large distinctions of anemia types and potential etiologies:
Microcytic (MCV < 80)
Normocytic (MCV 80-100)
Macrocytic (MCV >100)

Know how to interpret an iron panel in a medically ill patient:

1) Ignore the transferrin saturation

• Reason: does not discriminate between anemia of inflammation and iron deficiency

2) Assess ferritin

• <20: Iron deficiency
• 20-100: Iron deficiency likely if inflammation, chronic viral infection, etc.
• 100-800: Unlikely iron deficiency (unless hepatitis, chronic HD)
• >800: Extremely unlikely iron deficient

3)Assess the TIBC (preferred over transferrin level)

• >400: Iron deficient
• 300-400: Likely a component of iron deficiency
• 200-300: Unlikely iron deficient
• <200: Very unlikely iron deficient, usually inflammation, liver failure

Tuberous Sclerosis:

• Autosomal dominant genetic disorder due to a mutation in either TSC1 or TSC2 gene.
• Incidence of 1 in 5000-10000 live births
• De novo mutations account for ~ 80% of TSC cases
• TSC is highly variable in expression – thus the severity of disease can vary substantially among affected individuals within the same family
• TSC is characterized by the development of a variety of benign tumors in multiple organs: brain, heart, skin, kidney, lung, and liver

81-95% of TSC patients have on the characteristic skin lesions:

• Angiofibromas ~ typically on the malar region of the face
• Hypopigmented macules AKA ash-leaf spots ~ elliptic in shape
• Shagreen patches ~ usually over the lower trunk
• A distinctive brown fibrous plaque on the forehead ~ usually the first and most readily recognized feature of TSC
• Periungual/subungual fibromas develop during adolescence or adulthood; toenails > fingernails

CNS lesions characteristic of TSC include:

• Glioneuronal hamartomas (corticol tubers)
• Subependymal nodules
• Subependymals giant cell tumors (SGCTs): the characteristic brain tumor of TSC with a prevalence of ~ 5-20%, with 6-9% symptomatic

Neurological complications include:

• Seizures ~ 79-90% of patients, most often in the 1st year of life
• Cognitive deficits ~ 44-65%, associated with a history of infantile spasms or refractory seizures
• Behavioral problems ~ 40-90%; typically hyperactivity, inattention, and self-injury

Cardiovascular complications include:

• Rhabdomyoma: a benign tumor that often presents as multiple lesions
• No evidence for malignant transformation; no treatment is necessary for asymptomatic tumors
• Unlike other lesions of TSC, cardiac rhabdomyomas often disappear in later life spontaneously

Renal complications include:

• Angiomyolipomas ~ 55-75% (estimated incidence)
• Benign tumors composed of abnormal vessels, immature smooth-muscle cells, and fat cells
• Due to the abnormal vasculature and potential for aneurysms, spontaneously life-threatening bleeding is a potential complication

Pulmonary complication of TSC:

• Lympangiomyomatosis (LAM); Women (almost exclusively) – Widespread pulmonary proliferation of abnormal smooth-muscle cells and cystic changes within the lung parenchyma
• Two common intial manifestations of LAM: dyspnea and spontaneous pneumothroax

Diagnostic criteria for TSC:

Diagnosis is based on either genetic testing results and/or clinical findings

Genetic criteria:

• Identification of either a TSC1 or TSC2 pathogenic mutation (i.e. a mutation that clearly inactivates the function of TSC1/2 proteins)

Clinical criteria:

• 11 major and 6 minor features
• Definite diagnosis requires 2 major or 1 major/>2 minor features

Management of TSC:

• Requires a multidisciplinary approach of specialists including: neurologists, dermatologists, geneticists, and pulmonologists
• Referral to a TSC clinic is recommended given the complexity of the disease (next slide)
• Long-term follow-up including monitoring of lesion growth (angiomyolipomas and SGCTs); no conclusive guidelines exist
  • Standard practice: brain/abdominal imaging every 3 years; more frequently with known lesions
  • Genetic counseling for family planning (risk of affected child is 50%)

Therapeutic Options:

• Sirolimus (mTOR inhibitor) has been identified as a potential option given tumor cells from patients with TSC active mTOR (studies ongoing)

Risk Factors for PJP (Pneumocystis Jiroveci) Pneumonia

-Advanced immunosuppression (esp. HIV with CD4 count <200), hematologic malignancy, s/p BMT
-Previous episodes of PCP
-Oral thrush
-Recurrent bacterial PNA

Timing

–SUBACUTE indolent symptoms (on average, ~3 weeks)-not as acute as bacterial PNA!

S&S

-Progressive exertional dyspnea (95 % of patients)
-Fever (90 % of patients)
-Non-productive cough (90 % of patients)
Pearl: make sure you walk your patients with suspected PCP as it will reveal their hypoxemia!

Labs to obtain to suggest diagnosis

-HIV (look for CD4 count <200, off Bactrim prophylaxis)
-ABG to evaluate for A-A gradient and hypoxemia
-LDH (elevated LDH has high specificity/low sensitivity)
-1,3 Beta D Glucan (>80 can support diagnosis, but not specific)

How do you make the diagnosis?

-Must visualize the cystic/trophic form directly, cannot be cultured
-Use a SILVER stain to make the diagnosis

Step 1: Sputum induction (sensitivity 55-90 %, specificity 100 %). If negative, go to step 2!
Step 2: Bronchoalveolar Lavage, 90-100 % sensitivity.

If still negative, lung biopsy has a sensitivity/specificity of 90-100 % but very invasive!

Treatment 

Bactrim 15-20 mg/kg x 21d

When do you add adjunctive steroids?

Only for moderate to severe hypoxemia! 
If PaO2<70, or A/A gradient >35, treat with Prednisone 40 PO BID x 5d, 40 mg PO daily x 5d, 20 mg PO daily x 11d.

See article here by NEJM and Cochrane study on the use of steroids in PCP.

 

 

GBS
-There are multiple variants of GBS!

-AIDP (Acute inflammatory demyelinating polyneuropathy)- 85-95 % of GBS
-Miller Fisher Variant (5 % US but up to 25 % in Japan)
-AMAN (Acute motor axonal neuropathy)
-AMSAN (Acute sensorimotor axonal neuropathy)

Timing

Acute (<4 weeks)

Pathophysiology

Due to molecular mimicry from immune response to preceding infection that cross reacts with components of the peripheral nerve.

Most common infectious triggers?
-Campylobacter Jejuni (most common), CMV, EBV, HIV, VZV, Mycoplasma, and even Zika virus

Most sensitive physical exam findings in GBS

-Absent/Depressed DTR (90 %)
-Ascending extremity weakness (90 %)
-Paresthesias (80 %)
-Dysautonomia (70 %)
-Facial weakness or bulbar signs (55 %)
-Back/extremity pain, respiratory failure, oculomotor weakness

What do you see on LP?

Albumino-cytologic dissociation (normal WBC with high protein)

HOWEVER, only 50 % of patients with GBS have it at one week, with >75 % of patients have it at 3 weeks so make sure you interpret it in the right clinical setting

Miller Fisher variant TRIAD (don’t need to see all three)

-Ophthalmoplegia
-Ataxia
-Areflexia
Antibodies against GQ1b (anti-ganglioside) present in 85-90 % of patients- however, this will take a long time to come back and won’t change your initial management.

Treatment

-Supportive treatment
-IVIG 
-Plasma Exchange

Remember that steroids are not effective!

 

Remember Light’s Criteria is SENSITIVE for picking up EXUDATES but mis-classifies ~25% transudative effusions as exudative!
-You only need to have ONE of Light’s criteria to call it an Exudate!

TRANSUDATE
Remember the top 3 but there is an extensive list…

–CHF (most common)
-Hepatic hydro-thorax from cirrhosis
-Nephrotic syndrome

EXUDATE 
Remember the top 3 but also has an extensive list…

-Malignancy
-Pneumonia
-Tb

What percentage of patients with bacterial PNA get an associated effusion?
>40 % and up to 60 % with pneumococcal PNA, and can be either uncomplicated, complicated, or empyema

Uncomplicated parapneumonic effusion

-Resolves with antibiotic treatment of PNA
-On CXR, must be free-flowing and <10 mm
-Very low risk, does not need drainage 

Complicated parapneumonic effusion

-Small/Mod  in size, >10 mm but <1/2 hemithorax
-Negative gram stain/culture, pH>7.20
-May need drainage based on clinical status

Complicated parapneumonic effusion (second type)

-Large >1/2 hemithorax, LOCULATED, thickened parietal pleura (high risk if thickened parietal pleura, suspect Empyema) 
-Positive culture or gram stain OR
-pH<7.20
-MUST drain effusion, moderate risk

EMPYEMA!

-defined as PURULENT appearance of pleural fluid OR
–pH <7.20 (don’t forget to order pH and keep it on ice!)
-If ether of these exist, MUST drain effusion, highest risk, usually with tube thoracostomy (chest tube)

Treatment

-Empiric therapy should cover Gram + (eg: Staph, Strep), and Anaerobes (eg: Fusobacterium, Bacteriodes)
-Empyema is treated with 4-6 weeks of antibiotic treatment

Etiologies of a PROLONGED Qtc (not an exhaustive list) 
Remember that many LOW electrolytes can lead to prolonged Qtc increasing risk of arrhythmias (usually Torsades)

–Drugs  (large category, includes anti-psychotics, anti-arrhythmics,TCA, anti-histamines)
-HYPOkalemia
-HYPOmagnesemia
-HYPOcalcemia
-HYPOthermia
-Congenital (eg: long QT syndrome)

What can cause HYPOcalcemia?

-HYPOparathyroidism (PTH controls calcium and phosphorus homeostasis)
-HYPOproteinemia (Pearl: always check albumin with calcium unless you are checking ionized calcium!~0.8 increase in calcium for every 1.0 decrease in albumin from 4.0)
–Renal disease (remember that the kidney makes activated Vit D with 1 alpha hydroxylase and Vit D absorbs calcium from the gut)
-Vit D deficiency (cannot absorb calcium)
-Hyperphosphatemia (binds calcium and lowers serum levels, is the etiology of hypocalcemia in Rhabdo and TLS)
-Acute Pancreatitis
-Chelation (eg: after being given Citrate/EDTA/Foscarnet)
-Hypomagnesemia (Mg needed for PTH activity)
-Hungry bone syndrome (seen after parathyroid surgery for elevated PTH where bones start sequestering the calcium levels in the serum)

Clinical manifestations of HYPOcalcemia

Remember CATS mnemonic!

NEUROMUSCULAR IRRITABILITY 

-Parethesias
-Tetany
-Trousseau’s sign-carpopedal spasm seen when inflating BP in upper arm above systolic pressure (highly sensitive and specific!)
-Chvostek’s sign- facial twitching in response to tapping over facial nerve (absent in one third of patients with hypocalcemia, and seen in 10 % of patients with normal calcium levels!)-Bronchospasm/Laryngospasm

CARDIAC

-Prolonged Qtc, Arrhythymia
-Hypotension, HF

NEUROLOGIC

-Seizures
-Extra pyramidal symptoms (eg: Parkinsonism)
-Irritability, depression, personality changes

PRIMARY vs. SECONDARY vs. TERTIARY HPT 

Where does the problem start? 

Primary– Elevated PTH is the problem leading to high Ca, low Phos
Secondary-LOW calcium is the problem leading to elevated PTH
Tertiary-PTH is again the problem but it is functioning autonomously due to uncontrolled secondary PTH or post-renal transplant so calcium is elevated but phosphorus still elevated due to renal failure.

NuvaRing:

• Combined (progestin/estrogen) hormonal contraceptive vaginal ring
• Works by preventing ovulation and inhibition of sperm penetration (via cervical mucosal changes)
• Used for a 3 week period followed by a “break week;” reported 91% effective with typical use

Appendicitis:

Epidemiology: Most common indication for emergent abdominal surgery in childhood (<14 years old); Males > Females.

Pathophysiology: Non-specific obstruction of the appendiceal lumen (fecal material, undigested food, enlarged lymphoid follicle, etc.)

Clinical Manifestations: Anorexia, periumbilical pain (early) → migration to RLQ (often within 24 hours), vomiting (after onset of pain), fever (24-48 hours after symptoms)

Diagnosis: Clinical diagnosis; various scoring systems to aid treatment (PAS,    Alvarado score, etc.), CBC (leukocytosis), +/- imaging (US vs. CT)

Treatment: Surgical resection

Pelvic Inflammatory Disease (PID):

Epidemiology: Sexually active females, younger age (15-25 yo), prior STIs, previous PID are all known risk factors; method of contraception also important (barrier is protective)

Pathophysiology: Two stages: Stage 1) acquisition of a vaginal or cervical infection (often STI); Stage 2) direct ascent of microorganism

Clinical Manifestations: Fever, nausea/vomiting, severe pelvic/abdominal pain, abnormal vaginal discharge (75% of cases), unanticipated vaginal bleeding, tenderness on pelvic exam (adnexal tenderness 95% sensitive)

Diagnosis: History/Physical, pregnancy test, CBC (leukocytosis), saline microscopy of vaginal fluid, ESR/CRP, STI testing, UA, +/- imaging

Treatment: Antibiotics against common organisms:

• Regimen A: ceftriaxone, doxycycline, metronidazole
• Regimen B: cefoxitin, doxycycline, metronidazole

Ectopic Pregnancy:

Epidemiology: Increased incidence (4.5/1000 pregnancies in 1970 vs. 19.7/1000 in 1992) attributed to improved diagnostics; more common in women > 35 years old and non-white ethnic groups.

Pathophysiology: Any pregnancy in which the fertilized ovum implants outside the intrauterine cavity (>95% in the fallopian tubes)

Clinical Manifestations: Abdominal pain with spotting ~ 6-8 weeks after the last menstrual period; physical findings include slightly enlarged uterus, pelvic pain with movement of the cervix, and palpable adnexal mass

Diagnosis: History/Physical, pregnancy test, +/- progesterone, US

Treatment: Depends on patient stability:

1. Expectant management: 68-77% resolve without intervention
2. Medical management: methotrexate
3. Surgical resection: salpingectomy via laparotomy

Ovarian Torsion:

Epidemiology: 5th most common surgical emergency in females; primary risk factor is an ovarian mass (particularly >5cm) or pregnancy (20%), can occur at any age – but most common in early reproductive years (median age 28 years)

Pathophysiology: Ovary rotates around both the suspensory and utero-ovarian ligament; rotation results in compression of the ovarian vessels (vein before artery) leading to ovarian edema and eventually ischemia

Clinical Manifestations: Classic presentation: acute onset of moderate-severe pelvic pain (90%), often with nausea/vomiting (47-70%), in a women with an adnexal mass (86-95%); other symptoms include fever (2-20%) and abnormal vaginal bleeding (4%)

Diagnosis: History/Physical, pregnancy test, CBC, pelvic US with doppler

Treatment: Surgical evaluation with detorsion or resection

Yersina Enterocolitica:

Epidemiology: Most often due to consumption of raw or undercooked pork; young individuals more often (75% are 5-15 years old)

Pathophysiology: Following consumption, invasion and penetration occurs in the ileum (M cell) => multiplication in Peyer patches (underlying lymphoid tissue) => mesenteric lymph => node spread => localized infection => systemic infection (rare)

Clinical Manifestations: Fever, abdominal pain, and diarrhea ~ 4-6 days after exposure; pain often localized to the right-side of the abdomen (pseudoappendicitis)

Diagnosis: History/Physical, stool culture for yersinia

Treatment: Supportive care typicially; aminoglycosides and TMP-SMZ if severe

Pyelonephritis:

Definition:

• Pyelonephritis is an infection of the upper urinary tract, specifically the renal parenchyma and renal pelvis
• Cystitis refers to an infection of the lower urinary tract, specifically the bladder

Epidemiology:

• Women > Men (11.7 vs 2.4 hospitalizations per 10,000 cases)
• Men > Women (16.5 vs 7.3 deaths per 1000 cases)

 

	PID	Cystitis	Pyelonephritis
Dysuria	+	+	+
Discharge	+
Abdominal Pain	+	+	+
Fever	+		+
Frequency/Urgency	+	+	+
CMT	+
CVA			+

Pathogenesis:

• Most renal parenchymal infections result from bacterial ascent through the urethra and urinary bladder
• In males – prostatitis and prostate hypertrophy (causing urethral obstruction) predispose to bacteriuria

Uncomplicated Pyelonephritis:

1. Typical pathogen
2. Immunocompetent patient
3. Normal urinary anatomy/renal function

Treatment:

Outpatient:

• Oral fluoroquinolone (i.e. ciprofloxacin)
• Recommended given low resistance rates (1-3%), absorbed well from the GI tract, excellent kidney penetration
• Other acceptable options for susceptible organisms include:

1. Amoxicillin-clavulanate (preferred for pregnancy)
2. Cephalosporin
3. Trimethoprim-sulfamethoxazole

Inpatient:

• IDSA recommends one of three IV therapies:

1. Fluoroquinolone (i.e. ciprofloxacin)
2. Aminoglycoside (i.e gentamycin) +/- ampicillin
3. Extended-spectrum cephalosporin +/- aminoglycoside

• 7-14 days is effective; but studies suggest that 5-7 is comparable to longer duration in terms of clinical and bacteriologic outcome
• Therapy with appropriate empiric antibiotics should produce improvement within 48-72 hours; failure should additional testing for an alternative diagnosis

Risk factors for developing Infective Endocarditis 

-Recent dental/surgical procedure
-Prosthetic valve
-Valvular or congenital heart disease
-IVDU
-Indwelling IV catheter
-Immunosuppression

Signs and Symptoms of Endocarditis

-Fever (90 % of patients!)
-Murmur (85 % of patients)
-Petechiae (20-40 % of patients)
–Splinter hemorrhages (~10-15 %)
–Splenomegaly
–Janeway lesions-Non-tender, erythematous MACULES on palms and soles
–Osler nodes- tender, subcutaneous violaceous NODULES, usually on pads of finger and toes
–Roth spots– exudative edematous hemorrhages in retina with pale centers

*Remember that peripheral findings are uncommon (<10 %) unless protracted and untreated bacteremia

Indications for surgical repair in endocarditis

-CHF (eg: worsening valvular involvement)
-Perivalvular extension (eg: abscess, development of AV block)
-Systemic embolism
-Prosthetic valve
-CVA
-Persistent sepsis
-Resistant organism (eg: Staph aureus, pseudomonas, fungus)
-Large vegetation (>10-15 mm)

Common organisms implicated in Endocarditis (not an exhaustive list) 

-HACEK organisms (found in oral-pharyngeal region, Haemophilus, Aggregatibacter (previously Actinobacillus), Cardiobacterium, Eikenella, Kingella)
-Staph aureus (most common cause in IVDU)
-Coagulase negative staph
-Strep Gallolyticus (formerly known as Strep Bovis)
-Viridans Strep
-Enterococci

 

Remember the different types of HIT:

	Type 1	Type 2
Mechanism	Direct effect of heparin (non-immune)	Immune (Ab)-mediated IgG against platlet factor 4-heparin complex
Incidence	10-20%	1-3% with UFH; 0-0.8% with LMWH
Onset	After 1-4 day of heparin therapy	After 4-10 day; but can occur <24 h if prior exposure w/in 100 days (persistent Ab). Postop highest risk. Can occur after heparin d/c’d
Platelet nadir	>100,000/μL	~60,000/μL, ê 50%
Sequelae	None	Thrombotic events (HITT) in 30-50%; rare hemorrhagic complications
Management	Observe	Cessation of heparin, alternative non-heparin anticoagulation to prevent thrombosis

Pathophysiology:

1. Autoantibodies (IgG) are formed to platelet factor 4 (PF4) complexed with heparin
2. Platelet Fc receptors bind the antibody-heparin-PF4 immune complex

• Thrombocytopenia occurs by two mechanisms:

1) Platelet removal by splenic macrophages
2) Platelet consumption due to thrombus formation

Clinical Variability:

• 10 times higher incidence with UFH compared with LMWH
• A metaanalysis of 15 studies (>7000 patients) that evaluated the risk of HIT with prophylactic UFH vs LWM found the following absolute risks of developing HIT
• UFH – 2.6% (95% CI 1.5 – 3.8%)
• LMH – 0.2 % (95% CI 0.1 – 0.4%)
• Surgical > Medical patients; Incidence is particularly high after orthopedic surgery

Risk Factors:

• There is no dose of heparin that is too low to cause HIT! Patients have developed HIT after exposure to as little as 250 U flush.
• Female sex appears to be at a higher risk for unclear reasons – this was based on 7 trials comparing UFH vs LWH found approximately twice the risk.

Clinical Manifestations:

• Thrombocytopenia (<150,000/microL ~ 85-90%)
• Platelet drop of >50% is typical with mean nadir of 60,000/microL and RARELY <20,000/microL
• Typical onset is 4-10 days after heparin therapy
• Patients with exposure to heparin in the previous 100 days can develop a early onset (<24 hours) HIT
• Thrombosis occurs in up to 50% of HIT patients (venous > arterial); presenting finding in up to 25%
• Thrombotic sequelae – skin necrosis, limb gangrene, organ ischemia/infarction

4T Score:

• A total score <4 points has a very high negative predictive value (97-99%); additional testing is not necessary

Assuming an intermediate/high risk score – what other labs can aid in the diagnosis:

• Anti-PF4 heparin antibodies – excellent NPV (98-99%), but low PPV due to presence of clinically insignificant antibodies (IgM, IgA)
• Our lab restricts the antibodies to only IgG – which increases the specificity
• Also provides an optical density (magnitude of anti-PF4-heparin reactivity) ~ greater activity (>2.0) correlates to a greater likelihood of HIT
• Serotonin-release assay – functional assay that measures heparin-dependent platelet activation; a negative result rules out HIT

Treatment:

Step 1: Immediate cessation of heparin

Step 2: : Initiation of an alternative anticoagulant at a therapeutic dose.

• Vitamin K antagonists should NOT be given until HIT has resolved (i.e. platelets > 150,000 for >2 days) because they increase the risk of venous limb gangrene/limb loss by decreasing levels of protein C.
• Argatroban (direct thrombin inhibitor) is the only currently FDA approved medication in the US.  Danaparoid (anti-factor Xa) is approved in Canada, EU, and Australia.  Other options include: Lepirudin and Bivalrudin.