Emergencies in Hematology

Zwi Berneman

BHS Educational Course

Seminar 4: Supportive Care in Hematology

15 February 2014

Emergencies in Hematology (I)

• Severe anemia: due to bleeding or

hemolysis

• Febrile neutropenia

• (Bleeding due to) severe thrombocytopenia

• (Bleeding due to) clotting disorders

Thrombocytopenia

TRC < 140 x 109/l; danger if < 10 (-20) x 109/l TRC transfusion (also TRC transfusion if trombocytopenia > 10 x 109/l and overt bleeding).

Diagnosis:

• Peripheral blood: MPV ? Other anomalies? (RBC, WBC?); schistocytes (≥0.5-1%): TTP/HUS or DIC?

• Clotting: APTT, PT, fibrinogen, D-dimers (DIC?)

• Bleeding time not necessary.

• Bone marrow: peripheral or central origin of thrombocytopenia?

• (Auto-antibodies: ANF, anti-CCP, …; TRC antibodies not in current use anymore).

Thrombotic thrombocytopenic purpura (TTP)(/Hemolytic uremic syndrome (HUS))

Pathology (pentade): microangiopathic hemolytic anemia; thrombocytopenia; neurologic abnormalities; renal failure; fever.

TTP(/HUS): clinical diagnosis; requires only thrombocytopenia and microangiopathic hemolytic anemia.

Disseminated intravascular coagulation (DIC): usually not at start of TTP/HUS (APTT, PT, fibrinogen usually not disturbed in a major way at start of TTP/HUS).

Differential diagnosis of TTP/HUS, DIC, HELLP syndrome and postpartum renal failure difficult in obstetric circumstances.

TTP (/ HUS)Etiology:

• Severe (<10% activity) ADAMTS13 deficiency

• Typical or acute diarrheal HUS: associated with

enterotoxicogenic E. coli or Shiga toxin-producing E.

coli (STEC-HUS) – in children

• Atypical HUS: mutation in complement.

Therapy in the acute setting:

• Plasmapheresis: urgent, especially if neurological

symptoms; do not wait for the results of ADAMTS13

levels!

• According to some: preferably no thrombocyte

transfusions, unless bleeding or invasive procedure.

Disseminated intravascular coagulation (DIC)

No primary disease entity, with usually a

demonstrable etiology.

Clinical presentation (1):

• Bleeding: generalized, unexplained

• Renal failure

• Hypoxia

• Neurological features (CNS bleeding,

thrombosis).

DIC

Clinical presentation (2)

Variants with thrombosis:

• Trousseau syndrome: recurrent thrombosis

(venous and arterial) – (hidden)

malignancy?

• Purpura fulminans : (cutaneous) DIC +

necrosis.

DIC

Diagnosis

• APTT usually (can be normaal)

• PT usually disturbed (INR ) (can be normal)

• Fibrinogen or decreasing

• D-dimers +

• Thrombocytes

• RBC fragmentation – schistocytes (50-60% of

cases)

DIC

Etiology

• Septicemia (Gram- > Gram+)

• Neoplasia: procoagulant substance

• Obstetric complications (placenta previa, abruptio

placentae, mors in utero, amniotic fluid embolism,

abortus)

Differential diagnosis with HELLP syndrome:

hemolysis, elevated liver tests, low platelets ((pre)-

eclampsia).

• Other: trauma, peritoneovenous shunt, hemangioma,

pancreatitis, heat stroke, aneurisma, snake bites.

DIC – Treatment (1)

Treat the cause; treat also hypotension, hypoxia,

hypovolemia, acid-base and electrolyte

disturbances.

• DIC with bleeding:

– Freshly frozen plasma (FFP)

– TRC transfusions (check increase in TRC count)

– (Antithrombin (III))

– Heparin: controversial; only as last resort if nothing

else helps.

DIC – Treatment (2)

DIC with thrombosis: heparin

Trousseau syndrome

Purpura fulminans

Mors in utero

Amniotic fuid embolism

Emergencies in Hematology (II)

• Hypercalcemia (myeloma, lymphoma)

• Spinal cord compression (myeloma,

lymphoma)

• Obstructive nephro-uropathy (lymphoma)

• Malignant pericardial effusion (lymphoma,

acute leukemia).

• Vena cava superior syndrome (lymphoma)

Emergencies in Hematology (III)

• Hyperviscosity syndrome:

– paraprotein (Waldenström’s macroglobulinemia, myeloma)

– RBC (polycythemia vera)

– WBC (leukostasis)

Hyperviscosity syndrome

• Waldenström’s macroglobulinemia

(lymphoplasmocytic lymphoma with IgM

hypersecretion) >> IgA myeloma > IgG myeloma

• Symptoms: visual, neurological, cardial, bleeding.

• Eye fundus examination: “linked sausage effect”of the retinal veins, retinal bleeding, exsudation.

• Treatment: plasmapheresis in symptomatic

hyperviscosity; chemotherapy

Leukostasis

(symptomatic hyperleukocytosis)

Hyperleukocytosis (WBC > 50-100x109/L) with

respiratory and/or neurological distress.

Covers 2 pathological processes:

• Organ dysfunction due to hyperviscosity and

tissue hypoxia caused by hyperleukocytosis

• Proliferation of leukemic cells through blood

vessel endothelium, formation of tumors and

secundary bleeding.

Frequency: AML, CML-BC > CML-CP, ALL>CLL

Leukostasis

Occurrence:

• Lungs > brain > liver, kidneys, genito-urinary tract

• In acute leukemia, CML-BC: WBC > (50) -100 x 109/L

• In CML-CP: > 300 x 109/L

• In CLL: > 400-800 x 109/L.

Diagnosis: eye fundus examination.

If left untreated: 1-wk mortality rate 20-40%

Leukostasis: Treatment

• Prompt institution of (induction) chemotherapy

• Patients who must have induction chemotherapy delayed:

– Asymptomatic hyperleukocytosis: hydroxyurea 50-100 mg/kg/day (eg. 2-4 g/12 hr) – reduces WBC by 50-80% within 24-48 hr

– Symptomatic hyperleukocytosis: hydroxyurea + leukapheresis ; per leukapheresis: reduction of WBC with @ 30%; NOT in acute promyelocytic leukemia. [Conflicting data of effect of leukapheresis on early mortality not recommended as routine treatment].

• Delaying RBC transfusions; TRC transfusions during leuphapheresis; prevention & treatment of tumor lysis syndrome, DIC and renal damage.

Emergencies in Hematology (IV)

Tumor lysis syndrome

Rapid lysis of tumoral cells with release of intracellular phosphate, potassium and uric acid.

Potential consequences:

• hyperuricemia (nephropathy, gout)

• hyperkaliemia (cardiac dysrythmia)

• hyperphosphatemia (hypocalcemia, progressive renal failure)

• hypocalcemia (muscle spasms, cardiac dysrythmia).

Tumor lysis syndrome

Treatment and prevention:

• rasburicase (Fasturtec): recombinant urate

oxidase

• allopurinol

• correction of electrolyte anomalies

• (Early dialysis, if needed).

Illustrations from:

AV Hoffbrand, JE Pettit. Color Atlas of

Hematology. London: Mosby, 3rd edition,

2000