Medical Emergencies In Hematology

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Discussed emergencies (10)

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Superior vena cava syndrome
Leukostasis – symptomatic hyperleukocytosis
Hyperviscosity syndrome
Tumor lysis syndrome
Hypercalcemia
Febrile neutropenia
Immune thrombocytopenia
Heparin-induced thrombocytopenia
Warfarin associated coagulopathy
DIC

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SVC syndrome
def?
signs / symptoms?

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Denotes compression, obstruction or thrombosis of the superior vena cava

Signs and symptoms
Dyspnea
Cough
Dysphagia
Orthopnea
Chest pain
Headache
Facial and neck edema
Venous distention in the neck and distended veins in the upper chest and arms
Upper limb edema
Pleural and pericardial effusions

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Causes of SVC syndrome?
Dx?

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Causes: Bronchogenic carcinoma (SCLC, NSCLC)
Hodgkin lymphoma
NHL - Primary mediastinal B cell lymphoma
- Burkitt´s lymphoma
- Lymphoblastic lymphomas
Acute lymphoblastic leukemias
Other tumours
Syphilis
Tuberculosis

Diagnosis: chest X ray - mediastinal widening
chest CT scan
lymph node biopsy/mediastinal mass

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Rx of SVC syndrome?

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Steroids (prednisone, methylprednisolone)

Chemotherapy- causal treatment in malignancies

Radiotherapy- causal treatment in malignancies

Prevention of tumor lysis syndrome (hydration, allopurinol…)

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Hyperleukocytosis
Leukostasis / Symptomatic Hyperleukocytosis
def?

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Hyperleukocytosis is WBC in peripheral blood ≥ 100 x 109/l.

Leukostatsis or symptomatic hyperleukocytosis:
Extremely elevated blast cell count and symptoms of decreased tissue perfusion (increased viscosity). White cell plugs are seen in the microvasculature. Damaged endothelium releases cytokines and toxins responsible for symptoms.

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Leukostasis / Symptomatic Hyperleukocytosis
Symptoms?

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Symptoms:potentially fatal complications:
neurological symptoms (headache, seizures, blurred vision, coma, CNS hemorrhage)
papilloedema
thrombosis
pulmonary leukostasis (dyspnea, cyanosis, hypoxia acidosis, pulmonary hemorrage)
GIT bleeding
metabolic derangement of tumor lysis

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What diseases can you find leukostasis?

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AML hyperleukocytosis 10% - 20% of pts (AML M4, M5 FAB) leukostasis - WBC≥ 100 x 109/l (large, poorly deformable blasts)

ALL hyperleukocytosis 10% - 30% (young adults)
leukostasis – rare

CLL hyperleukocytosis significant proportion of pts
leukostasis - rare unless WBC > 400 x 109/l

CML leukocytosis typical for pts
leukostasis very uncommon in chronic phase
can be seen in pts with myeloid blast crisis and elevated blast counts (WBC≥ 100 x 109/l)

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Hyperviscosity Syndrome
def?
symptoms?

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a group of symptoms triggered by increase in the viscosity of the blood

spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, and neurologic symptoms (headache, vertigo, seizures, coma)

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Hyperviscosity syndrome
etiology?

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increased level of protein- monoclonal gammopaties- Waldenstrom macroglobulinemia (IgM), multiple myeloma (IgG, IgA..)

high cell counts - polycythemia vera - elevated RBC leukemia -raised WBC

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Hyperviscosity syndrome
Dx?
Rx?

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serum viscosity (reference range: 1.4 -1.8 centipoises) hyperviscosity symptoms (≥5 centipoises)
or
symptoms of underlying disease (e.g.MM high paraprotein)

plasmapheresis and causal treatment of MM
leukapheresis and causal treatment of acute leukemia
polycytemia vera – phlebotomy and causal treatment of PV
adequate hydration

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Tumor Lysis Syndrome
def

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a group of metabolic complications occuring after treatment of cancer (lymphomas, leukemias), and rarely without treatment. The breakdown products of dying cancer cells cause hyperkalemia, hyperphosphatemia, hyperuricemia, hyperuricosuria, hypocalcemia, acute uric acid nephropathy and acute renal failure.

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Tumor lysis syndrome
When can it be seen?

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Manifestation: 12-72 hrs. after chemotherapy and or steroid treatment in Burkitt´s lymphoma
Lymphoblastic lymphomas Acute lymphoblastic leukemias
Less common: Hodgkin lymphoma, medulloblastoma,neuroblastoma

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Tumor lysis syndrome
What chemicals / compounds cause what damage?

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Hyperkalemia. High turnover of tumor cells leads to spill of potassium into the blood. Symptomatic hyperkalemia K> 6mmol/l: cardiac conduction abnormalities (can be fatal), severe muscle weakness or paralysis

Hyperphosphatemia causes acute renal failure in tumor lysis syndrome (deposition of calcium phosphate crystals in the renal parenchyma

Hypocalcemia. Calcium is precipitated to form calcium phosphate. Symptoms of hypocalcemia include:tetany, seizures, sudden mental incapacity, including emotional lability, parkinsonian (extrapyramidal) movement disorders, papilledema, myopathy

Hyperuricemia and hyperuricosuria. Acute uric acid nephropathy due to hyperuricosuria – a dominant cause of acute renal failure

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Other symptoms of Tumor lysis syndrome
Diagnosis is with Cairo-Bishop classification of uirc acid, potassium, phospates, calcium

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Abdominal pain
Spasms
Fullness
Anorexia
Vomiting
Back pain
Dehydration
Tetany
Seizures
Alteration in sensorium

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Tumor lysis syndrome
Diagnosis

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Diagnosis is with Cairo-Bishop classification of uirc acid, potassium, phospates, calcium.

Also creatinine, cardiac arrhythmias and SCD, seizures.

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Prevention of Tumor Lysis Syndrome

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Prophylactic oral or IV allopurinol (a xanthine oxidase inhibitor, which inhibits uric acid production)

Adequate IV hydration to maintain high urine output (> 2.5 L/day)

Rasburicase (Uricase) - an alternative to allopurinol (a synthetic urate oxidase enzyme and acts by degrading uric acid

Alkalization of the urine with acetazolamide or sodium bicarbonate is controversial. Routine alkalization of urine above pH of 7.0 is not recommended. Alkalization is also not required if uricase is used.

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Treatment of Tumor Lysis Syndrome

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Treatment of metabolic disorders: hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia

Acute renal failure prior to chemotherapy (the cause of ARI is uric acid build-up), therapy consists of rasburicase to wash out excessive uric acid crystals and loop diuretic and fluids
Not responding pts – hemodialysis

Acute renal failure after chemotherapy (the cause of ARI is hyperphosphatemia), treatment is hemodialysis

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Hypercalcemia
def

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Elevated calcium level in the blood (normal range: 2.2–2.65 mmol/l)
Medical emergency: severe hypercalcemia (3.75–4 mmol/l)

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Hypercalcemia
symptoms and signs

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Signs and symptoms
Renal or biliary stones
Bone pain
Abdominal pain, constipation, anorexia, nausea, vomiting
Polyuria
Depression, anxiety, cognitive dysfunction, insomnia, drowsiness, confusion, hallucinations, stupor, coma
Hypotonicity of smooth and striated muscle, muscle weakness, low tone and sluggish reflexes in muscle groups
Fatigue
Arrhytmias, ECG: short QT interval, widened T wave, cardiac arrest
Increased gastrin production- increased acidity-peptic ulcers

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Hypercalcemia
causes

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Malignancies
Hematologic malignancies (multiple myeloma, lymphoma, leukaemia)
Solid tumour with metastasis (e.g. breast cancer or squamous cell carcinoma)
Solid tumour with humoral mediation of hypercalcemia (e.g. NSCLC or kidney cancer, phaeochromocytoma)

Abnormal parathyroid gland function

Vitamin-D metabolic disorders

Disorders related to high bone-turnover rates

Renal failure

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Treatment of Hypercalcemia

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Hydration and forced diuresis (loop diuretic- furosemide)

Bisphosphonates
They are taken up by osteoclasts and inhibit osteoclastic bone resorption
Pamidronate or zoledronate i.v.
All patients with cancer-associated hypercalcemia should receive treatment with bisphosphonates

Calcitonin
Cacitonin blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption

Steroid treatment
-increase urinary calcium excretion and decrease intestinal calcium absorption

Hemodialysis
- in severe hypercalcemia complicated by renal failure

Phosphate therapy
- can correct the hypophosphataemia in the face of hypercalcemia and lower serum calcium

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Febrile Neutropenia

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absolute neutrophil count (ANC) < 0.5x109/l or ANC< 1.0x109/l with expected decline accompanied with fever

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Immune thrombocytopenia
Main sign?
Secondary causes

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Bleeding
HCV, HIV, H.pylorus, pregnancy

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Heparin-induced thrombocytopenia
onset?
def?
other signs?
diagnosis?

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5-14 days after heparin administration, or 48 hrs after if previous heparin exposure within last 100 days.
Anaphylactoid reaction may take place within 30 min.

fall in platelet count with 50%

Venous or arterial thromboses, absence of petechiae, skin necrosis

Immunologic tests if there are antibodies, especially PF4. Functional tests if these antibodies are capable of activating platelets.

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Warfarin associated coagulopathy management in
a) Difficult-to-control INR

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1. Question and control for common causes of INR variability.
2. Consider low-dose daily vitamin K supplementation

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Warfarin associated coagulopathy management in
b) The nonbleeding patient
INR 3.0–4.5
INR 4.5–10
INR above 10

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1. Warfarin withdrawal or dose adjustment
2. Consider preoperative vitamin K 1 mg p.o. if INR elevated the day before surgery, and recheck INR on day of operation

1.Warfarin withdrawal or dose adjustment
2. Consider vitamin K 1 mg p.o. (or 0.5 mg iv.)
3. Close monitoring for INR and signs of bleeding

1. Warfarin withdrawal or dose adjustment
2. Vitamin K 2.0–2.5 mg p.o. (or 0.5–1 mg iv.)
3. Close monitoring for INR and signs of bleeding

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Warfarin associated coagulopathy management in
c) The bleeding patient
Minor bleeding
Major bleeding

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1.Warfarin withdrawal ± dose adjustment
2.Correction of the underlying defect (e.g., compression, packing, topical antifibrinolytics)
3.Vitamin K 2.5–5 mg p.o., with possible repeat dose after 24 h if incomplete correction

1.Warfarin withdrawal ± dose adjustment
2. Correction of the underlying defect (e.g. compression, packing, topical antifibrinolytics)
3. Factor replacement with PCC or FFP
4. Vitamin K 10 mg iv. via slow infusion

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Disseminated intravascular coagulopathy
what happens/ what is it?

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Pathological activation of coagulation (blood clotting) in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood vessels throughout the body.

Small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs from the skin, GIT, respiratory tract and surgical wounds.

Small clots also disrupt normal blood flow to organs (kidneys) and may malfunction as a result.

Acute or chronic DIC

Development of multiple organ failure and death

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Disseminated intravascular coagulopathy
mediators of DIC

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tissue factor (TF - present on the surface of many cell types)- exposed to the circulation after vascular damage. TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII)

release of endotoxin

malignancies enhance the expression of various oncogenes that result in the release of TF and plasminogen activator inhibitor-1 (prevents fibrinolysis)

Excess circulating thrombin results from the excess activation of the coagulation cascade. The excess thrombin cleaves fibrinogen - the resulting smaller clots form larger clots consuming more platelets and cause thrombosis. Coagulation inhibitors are also consumed in this process

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Causes of DIC

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Cancers of lung, pancreas, prostate and stomach, as well as acute myeloid leukemia (particularly APL)
Obstetric: abruptio placentae, pre-eclampsia, amniotic fluid embolism
Massive tissue injury: Trauma, burns, extensive surgery
Infections: Gram-negative sepsis, Neisseria meningitidis, Streptococcus pneumoniae, malaria, histoplasmosis, aspergillosis, Rocky mountain spotted fever

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Signs and Symptoms of DIC

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Signs of underlying disease
Hemorrhage and shock
Renal failure and subsequently multiorgan failure
Onset - fulminant (e.g.endotoxic shock or amniotic fluid embolism)
- insidious and chronic (carcinomatosis

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Diagnosis of DIC

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Thrombocytopenia
Prolongation of prothrombin time and activated partial thromboplastin time
A low fibrinogen concentration
A low antithrombin III
Increased levels of fibrin degradation products (D-dimers)

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Treatment of DIC

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Treatment of underlying disease (e.g. Sepsis, APL…)
Platelets may be transfused if counts are less than 5-10x109/l and massive hemorrhage is occurring
Fresh frozen plasma - to replenish coagulation factors
Fibrinogen
Antithrombin