HEMATOLOGICAL

EMERGENCIES-2
Ajay Kumar Yadav
PGY3,Medicine
IOM-TUTH, Kathmandu
LAYOUT
• Hyperleucocytosis and leucostasis

• Spinal cord compression

• Human Antibody Infusion Reactions

• Neutropenic enterocolitis
HYPERLEUCOCYTOSIS
AND
LEUCOSTASIS
INTRODUCTION
• Hyperleukocytosis : Refers to lab abnormality that has been variably defined as a total leukemia
blood cell count greater than 50,000/microL or 100,000/microL.

• Leukostasis : Aka Symptomatic Hyperleukocytosis

 Medical emergency

 Most commonly seen in patients with AML or CML in blast crisis.

 Characterized by an extremely elevated blast cell count and symptoms of decreased tissue
perfusion.
Cont..
• Leucostasis is a Pathologic diagnosis  white cell plugs are seen in the microvasculature.

• Clinically diagnosed empirically when a patient with leukemia and hyperleukocytosis presents
with respiratory or neurological distress.

• Prompt t/t is indicated since, if left untreated, the one-week mortality rate is approx. 20 to 40 pc.

• The frequency of hyperleukocytosis is 5–13% in AML and 10–30% in ALL.

EPIDEMIOLOGY
• AML:
• More common with myelomonocytic (FAB-M4) leukemia, monocytic (FAB-M5) leukemia, or
the microgranular variant of acute promyelocytic leukemia (FAB-M3) .
• Symptoms of leukostasis occur less frequently and typically affect pts with WBC counts over
100 x 109/L.

• ALL:
• The incidence appears to be highest in infants, patients between the ages of 10 and 20 years,
males, and those with a T cell phenotype
• Symptoms of leukostasis are rarely seen.
• TLS and DIC are more common complications related to the elevated WBC count.
• CLL
• Symptoms of leukostasis are rare unless the WBC count exceeds 400 x 109/L.

• CML
• Pts. with CML typically present with leukocytosis and a median WBC count of approx. 100 x
109/L
• Symptoms of leukostasis are very uncommon in chronic phase but can be seen occ. in
patients with myeloid blast crisis and very elevated blast counts.
PATHOPHYSIOLOGY OF LEUKOSTASIS
• There are two main theories, which are not mutually exclusive:

 Large population of leukemic blasts (less deformable than mature leukocytes) Increases blood
viscosity Plug microcirculation  impede blood flow (leukostasis).
 Worsened by RBC transfusions or the use of diuretics, both of which can increase whole
blood viscosity.

 Local hypoxemia may be exacerbated by the high metabolic activity of the dividing blasts and the
associated production of various cytokines Endothelial damage.

• Primitive myeloid leukemic cell are capable of invading through the endothelium and causing
hemorrhage.

• Brain(40 pc ) and lung(30 pc) are most commonly affected.

CLINICAL FEATURES
• Pulmonary involvement
• Dyspnea and hypoxia with/out diffuse interstitial or alveolar infiltrates on imaging studies.
• Arterial PaO2 can be falsely decreased in pts. with hyperleukocytosis, since the WBCs in the
test tube utilize oxygen.
• Pulse oximetry provides a more accurate assessment of O2 saturation in this setting.

• Neurological involvement
• Visual changes, headache, dizziness, tinnitus, gait instability, confusion, somnolence, and,
occasionally, coma.
• Increased risk of intracranial hemorrhage that persists for at least a week after the reduction
of white cell count, perhaps from a reperfusion injury as areas of the brain that were
ischemic from leukostasis regain blood flow.
Cont..
• Approx. 80 pc. of pts. with leukostasis are febrile, which may be due to inflammation associated with
leukostasis or concurrent infection.

• Less common s/s of leukostasis include

• ECG evidence of myocardial ischemia or right ventricular overload,

• Worsening renal insufficiency,

• Priapism,

• Acute limb ischemia, or

• Bowel infarction
LABORATORY ABNORMALITIES

• Pulse oximetry provides a more accurate assessment of O2 saturation.

• R/O Pseudo thrombocytosis : Manual counting

• R/O Pseudo hyperkalemia

• DIC occurs in up to 40 pc. of pts. : FDP and d-Dimer.

• Spontaneous TLS is present in up to 10 pc. of pts. with leucostasis : Uric acid, potassium,
phosphate, calcium and creatinine.
TREATMENT
• For pts with symptomatic or asymptomatic hyperleukocytosis
• Initial t/t with induction chemotherapy rather than hydroxyurea or leukapheresis.
• Accompanied by TLS prophylaxis with aggressive hydration and allopurinol.

• For pts without symptoms of leukostasis who must have induction chemotherapy delayed
• Cytoreduction with hydroxyurea rather than leukapheresis.
• Cytoreduction with hydroxyurea can ppt. or exacerbate hyperuricemia and/or TLS  IV
hydration and TLS prophylaxis.

• For pts with symptoms of leukostasis who must have induction chemotherapy delayed
• Initial cytoreduction with leukapheresis in combination with hydroxyurea to lower or stabilize
the WBC count.
Cont..
• Treatment of the leukemia can result in pulmonary hemorrhage from lysis of blasts in the lung,
called leukemic cell lysis pneumopathy.

• When APML is treated with differentiating agents like tretinoin and arsenic trioxide
• Cerebral or pulmonary leukostasis may occur as tumor cells differentiate into mature
neutrophils(Differentiation syndrome).
• This complication can be largely avoided by using cytotoxic chemotherapy or arsenic together
with the differentiating agents.
MALLIGNANTN SPINAL CORD
COMPRESSION(MSCC)
INTRODUCTION
• MSCC is defined as compression of the spinal cord and/or cauda equina by an extradural tumor
mass.

• The minimum radiologic evidence for cord compression is indentation of the theca at the level of
clinical features.

• Spinal cord compression occurs in 5–10% of pts with cancer.

• Epidural tumor is the first manifestation of malignancy in about 10% of pts.

• Lung cancer is the most common cause of MSCC.

Cont..
• Metastatic tumor involves the vertebral column more often than any other part of the bony
skeleton.

• Lung, breast, and prostate cancer are the most frequent offenders.

• Multiple myeloma also has a high incidence of spine involvement.

• Lymphomas, melanoma, renal cell cancer, and genitourinary cancers also cause cord
compression.

• The thoracic spine is the most common site (70%), followed by the lumbosacral spine (20%) and
the cervical spine (10%).

• Involvement of multiple sites is most frequent in patients with breast and prostate carcinoma.
• Direct extension of a paravertebral lesion through the intervertebral foramen : Lymphoma,
myeloma, or pediatric neoplasm.

• Parenchymal spinal cord metastasis due to hematogenous spread is rare.

• Intramedullary metastases can be seen in lung cancer, breast cancer, renal cancer, melanoma, and
lymphoma.
PATHOPHYSIOLOGY
• Obstruction of the epidural venous plexus leads to edema.

• Local production of inflammatory cytokines enhances blood flow and edema formation.

• Compression compromises blood flow, leading to ischemia.

• Production of vascular endothelial growth factor is associated with spinal cord hypoxia.
CLINICAL FEATURES
• Localized back pain and tenderness : MC presentation
• Involvement of vertebrae by tumor.
• Pain is usually present for days or months before other neurologic findings appear.
• Exacerbated by movement and by coughing or sneezing.

• Radicular pain : Less common

• Usually develops later.
• Radicular pain in the cervical or lumbosacral areas may be unilateral or bilateral.
• Radicular pain from the thoracic roots is often bilateral and is described by pts as a feeling of
tight, band-like constriction around the thorax and abdomen.
Cont..
• Lhermitte’s sign

• Loss of bowel or bladder control may be the presenting symptom but usually occurs late in the
course.

• Occasionally pts present with ataxia of gait without motor and sensory involvement due to
involvement of the spinocerebellar tract.
PHYSICAL EXAMINATION
• Pain induced by SLRT, neck flexion, or vertebral percussion may help to determine the
level of cord compression.

• Loss of sensation to pinprick is as common as loss of sensibility to vibration or position.

• The upper limit of the zone of sensory loss is often one or two vertebrae below the
site of compression.

• Motor examination
• Spastic weakness, spasticity
• Extensor plantar reflex and brisk DTR.

• Motor and sensory loss usually precedes autonomic dysfunction.

Cont..
• Autonomic dysfunction

• Present with decreased anal tonus, decreased perineal sensation, and distended bladder.

• The absence of the anal wink reflex or the bulbocavernosus reflex confirms cord involvement.

• Residual volume of >150 mL suggests bladder dysfunction.

MIMICKERS
• Osteoporotic vertebral collapse,
• AIDP,
• Pyogenic abscess or vertebral tuberculosis,
• Radiation myelopathy,
• Neoplastic leptomeningitis,
• Benign tumors,
• Epidural hematoma,
• Spinal lipomatosis.
• Cauda equina syndrome: characterized by

• Low back pain

• Diminished sensation over the buttocks, posterior-superior thighs, and perineal area in a saddle
distribution

• Bowel and bladder dysfunction; impotence

• Absent bulbo-cavernous and DTR.

• Variable amount of lower-extremity weakness.

• The majority of cauda equine tumors are primary tumors of glial or nerve sheath origin; metastases are
very rare.
IMAGING
• IOC
• Full-length image of the cord by Contrast MRI
• Myelography : Reserved for pts who have poor MRIs or who cannot undergo MRI promptly.

• CT Erosion of the pedicles (the “winking owl” sign) is the earliest radiologic finding.

• Other radiographic changes include

• Increased intra-pedicular distance,
• Vertebral destruction,
• Lytic or sclerotic lesions,
• Scalloped vertebral bodies, and
• Vertebral body collapse.
MANAGEMENT
• Goal of therapy
• Relief of pain
• Restoration/preservation of neurologic function

• Radiation therapy plus glucocorticoids is generally the initial t/t of choice.

• Up to 75% of pts treated when still ambulatory remain ambulatory, but only 10% of patients with
paraplegia recover walking capacity.
• INDICATIONS FOR SURGICAL INTERVENTION

• Unknown etiology,

• Failure of radiation therapy,

• Radioresistant tumor type (e.g., melanoma or renal cell cancer),

• Pathologic fracture dislocation, and

• Rapidly evolving neurologic symptoms

• TYPES OF SURGERY

• Laminectomy
• Posteriorly localized epidural deposits in the absence of vertebral body disease.

• Resection of the anterior vertebral body along with the tumor, followed by spinal stabilization
• Anterior or anterolateral epidural abscess.

• A RCT showed that pts who underwent surgery followed by radiotherapy (within 14 days)
retained the ability to walk significantly longer than those treated with radiotherapy alone.
• Chemotherapy may have a role in pts with chemosensitive tumors who have had prior
radiotherapy to the same region and who are not candidates for surgery.

• Patients with metastatic vertebral tumors may benefit from percutaneous vertebroplasty or
kyphoplasty, the injection of acrylic cement into a collapsed vertebra to stabilize the fracture.
• Pain palliation is common.
• Cement leakage seen in 10% of pts.
APPROACH TO PTS WITH MSCC
Cont..
HUMAN ANTIBODY INFUSION REACTIONS
• Seen with initial infusion of human or humanized antibodies (e.g., rituximab,
gemtuzumab, trastuzumab, alemtuzumab, panitumumab, brentuximab vedotin)

• A/w fever, chills, nausea, asthenia, and headache in up to half of treated pts.

• Bronchospasm and hypotension occur in 1% of pts.

• Severe manifestations including pulmonary infiltrates, ARDS , and cardiogenic shock

occur rarely.
• Lab manifestations include elevated hepatic aminotransferase levels, thrombocytopenia, and
prolongation of PT.

• Pathogenesis
• Activation of immune effector processes (cells and complement) release of inflammatory
cytokines, s/a TNF-α, INF-gamma, IL-6, and IL-10 (Cytokine Release Syndrome[CRS]).

• Treatment
• Diphenhydramine, hydrocortisone, and acetaminophen can often prevent or suppress the
infusion-related symptoms.
• If they occur, the infusion is stopped and restarted at half the initial infusion rate after the
symptoms have abated.
• Severe CRS may require intensive support for ARDS and resistant hypotension.
NEUTROPENIC ENTEROCOLITIS
INTRODUCTION
• Neutropenic enterocolitis (Typhlitis) is the inflammation and necrosis of the cecum and
surrounding tissues that may complicate the treatment of acute leukemia.

• Nevertheless, it may involve any segment of the GIT including small intestine, appendix, and
colon.

• Clinical presentation
• Right lower quadrant abdominal pain, often with rebound tenderness and a tense, distended
abdomen, in a setting of fever and neutropenia.
• Watery diarrhea (often containing sloughed mucosa)along with bleed.
• Bacteremia
DIAGNOSIS
• CT SCAN
• Marked bowel wall thickening, particularly in the cecum,
• Bowel wall edema,
• Mesenteric stranding, and
• Ascites

• Patients with bowel wall thickness >10 mm on USG have higher mortality rates.

• Pneumatosis intestinalis is a more specific finding, seen only in those with neutropenic
enterocolitis and ischemia.

• The combined involvement of the small and large bowel suggests a diagnosis of neutropenic
enterocolitis
TREATMENT
• Rapid institution of broad-spectrum antibiotics, bowel rest, and nasogastric suction.

• Surgical intervention

 Reserved for severe cases of neutropenic enterocolitis with

 Evidence of perforation,
 Peritonitis,
 Gangrenous bowel, or
 GI bleed despite correction of any coagulopathy
REFERENCE
• Harrison 19th Edition

• Wintrobe’s clinical hematology 13th edition

• UpToDate 2018
THANK YOU