Dr. Demeter Judit Semmelweis Egyetem ÁOK., I.sz. Belgyógyászati Klinika

Dr. Demeter JuditDr. Demeter Judit

Semmelweis Egyetem ÁOK., I.sz. Belgyógyászati KlinikaSemmelweis Egyetem ÁOK., I.sz. Belgyógyászati Klinika

Onchematologic emergenciesOnchematologic emergencies

Onkohematologic emergenciesOnkohematologic emergencies1.1. HemodynamicHemodynamic - vena cava superior syndrom- vena cava superior syndrom NHLNHL

- pericardial tamponade- pericardial tamponade lymphomaslymphomas- hyperviscosity syndrome- hyperviscosity syndrome MM, Wald.MM, Wald.- thrombosis- thrombosis myeloprolif.myeloprolif.

2.2. HematologicHematologic - bleeding- bleedingqualitative-quantitive pathologies of platelets qualitative-quantitive pathologies of platelets

ITPITPlack of coagulation factors DIClack of coagulation factors DIC (M3)(M3)

3.3. Nervous systemNervous system - spinal cord compression- spinal cord compression NHL, MMNHL, MMimmediate MR!immediate MR!

- koponyaűri nyomásfokozódás- koponyaűri nyomásfokozódás NHLNHL

4.4. MetabolicMetabolic - tumorlysis syndrome - tumorlysis syndrome hyperuricaemia, hyperkalaemiahyperuricaemia, hyperkalaemia

- hypercalcaemia- hypercalcaemia MM, NHLMM, NHL- hypokalaemia- hypokalaemia AMLAML- hypoglykaemia- hypoglykaemia insulinomainsulinoma

5.5. OtherOther - TTP/HUS- TTP/HUS

Incidence:

number of patients with hematologic and oncologic malignancies is increasing

The number of patients presenting with hemato-oncologic emergencies is expected to be increasing

Prospects:

patients cancer no longer should be looked upon as incurable and terminal even not even in the emergency departments

Patients are to some degree amenable to therapy or intervention

Following the succcesful treatment of an emergency condition, these patients may lead relatively normal lives.

1.neutropenic fever.

the most common !

2. mechanical emergenciesairway obstruction, superior vena cava syndromecardiac tamponadespinal cord compression.

3. metabolic emergencies.

hyperviscosity syndrome

hypercalcemia

syndrome of inappropriate antidiuretic hormone secretion (SIADH)

acute tumor lysis syndrome.

Often missed! superior sulcus lung tumor (Pancoast syndrome).

Infectious Emergencies

Neutropenic Fever

appropriate recognition and management may significantly lessen morbidity and mortality!

Neutropenia absolute granulocyte count is < 500 cells/µL

or < 1000 cells/µL with an anticipated decrease to < 500 cells/µL.

nadir mostly between 2-4 weeks after chemotherapy

Fever if if temperature exceeds >38.3° (101° F) or if the temperature = 38.0° C (100.4° F) for > 1 hour.

lack of circulating white blood cells.

few of the classic signs and symptoms of bacterial infections

e.g. significant pneumonia without cough or infiltrates on plain film. urinary tract infection

without WBC deposition in the urinary tract , lack of dysuria and frequency.

meningitis may present without clinical evidence of meningismus or cerebral spinal fluid pleocytosis.

Febrile neutropenia: cultures of blood and urine

chest x-ray performed (chest CT even better!)

if indwelling central line : at least one set of blood culture through it!

Immediate empiric antibiotic therapy!

( because progression of infection in neutropenic

patients may be very rapid)

Initial antibiotic therapy should be tailored to the suspected offending pathogens.

In the not too distant past, neutropenic patients were covered with two antibiotics, typically a third-generation cephalosporin in combination with an aminoglycoside. Traditionally, G-negative bacilli ( Pseudomonas, E coli, and Klebsiella): most common offending pathogens.

Nowadays: increase in the rate of infections caused by gram-positive bacteria, (some of them methicillin-resistant) .

Staphylococcus aureus

coagulase-negative staphylococci most common causes, particularly in patients with an indwelling catheter

Recommended: single agent antimicrobial therapy (monotherapy).

third or fourth-generation cephalosporin (ceftazidime or cefipime)

or a carbapenem (imipenem-cilastatin or meropenem)

. Include vancomycin in the treatment if:

• clinically-suspected serious catheter-related infections • known colonization with methicillin-resistant Staphylococcus aureus • positive results of blood culture for gram-positive bacteria before final

identification and susceptibility are known • hypotension or other clinical evidence of cardiovascular impairment

Growth factor treatment: filgrastim (Neupogen). stimulates WBC production

reduces the duration of neutropenia and fever, reduces the requirement of parenteral antibioticsreduces the duration of hospitalization. safe even in acute leukemia

Granulocyte transfusion not recommended!

1. initial antibiotic of choice:

third or fourth generation cephalosporin or a carbapenem.

(single agent therapy)

2. Cultures of blood and urine !

3. Consider chest CT if pulmonary symptoms present (active pulmonary infections may be present despite normal chest x-rays)

4. Vancomycin if indwelling intravenous catheter infection suspected

(in addition to gram-negative coverage).

5. rapid institution of empiric antibiotic therapy reduces morbidity and mortality.

6. reverse isolation room.  

Management of neutropenic fever

Mechanical Emergencies:

Spinal Cord Compression

any patient who presents with back pain may have spinal cord compression due to malignancy!

disseminated metastatic breast cancer to bone (after both chemotherapy and radiation therapy).

She developed paralysis and incapacitating pain.

MRI image: extensive bone tumor with collapse of the T10 and T11 vertebrae resulting in spinal cord compression.  

Epidural spinal cord compression

devastating complication of many malignancies

breast

lung

prostate cancer

AML (chloroma)

muItiple myeloma

Frequency ca. 5%

Importance of early detection in remaining ambulatory!

Epidural spinal cord compression

Might be the first clinical manifestation of malignancy.

Pts with known diagnosis of cancer (breast, lung, prostate, renal) + back pain

potentially lethal back pain entities

• cancer

• cauda equina syndrome

• abdominal aortic aneurysm,

back pain and a history of malignancy should be assumed to be metastasis to the spine or epidural spinal cord compression until proven otherwise

Presenting symptoms

numbness

tingling

sensory loss

bowel or bladder incontinence

abnormalities of proprioception e.g.loss of vibratory sense

back pain worsened by particular maneuvers, such as (coughing or lying in a supine position

pain that is worse at night.

New-onset radiculopathy from compression of a spinal root may also be the first manifestation of tumor (DDG: A herniated disc)

Epidural spinal cord compression

The physical examination may show evidence of spinal cord compression with paralysis or may be completely normal and unrevealing.

A detailed motor, sensory, and deep tendon reflex examination should be performed in all patients with suspected spinal cord compression, as well as observation of gait and evaluation of sphincter tone

Epidural spinal cord compression

think about the diagnosis in patients with back pain!

Dg-ic workup: Magnetic resonance imaging

epidural spinal cord compression can be subtle, and detection requires a high index of suspicion!

Treatment:

high dose corticosteroids - decompressive laminectomy - radiation

Epidural spinal cord compression

1. Pain may be the only finding !

Suspicious: Pain worsened by cough or the supine position

2. Physical examination: midline bony tenderness (often absent), ataxic gaitweaknessautonomic dysfunction (bowel or bladder incontinence).

3. Corticosteroids –iv. immediately!

4. Think about the diagnosis!

Epidural spinal cord metastasis and/or compression.

Superior Vena Cava Syndrome

becomes an emergency with the development of

cerebral edema (life-threatening cerebral herniation)

or

laryngeal edema (leading to airway compromise)

Causes: ( tuberculosis, aortic aneurysm, and fibrosing mediastinitis)

Nowadays: lung carcinoma lymphoma catheter-related superior vena cava thrombosis.

 Thickening of the prevertebral soft tissue shadow indicates laryngeal edema

Clinical manifestations:

protean

depend on the degree of vena cava obstruction.

Fom relatively asymptomatic with only mild facial fullness when bending forward or may have florid symptoms of facial swelling, headache, and airway compromise.

Superior Vena Cava Syndrome

A clue to the diagnosis is the presence of asymmetric neck, chest, or upper arm venous distension.

One diagnostic tool that has been employed by some is to compare the patient’s appearance to that of a picture of the patient, often a driver’s license

Subtle and sometimes marked changes in the physical appearance of the patient’s face can be identified.

The key to understanding the variability of the clinical presentation is the anatomy of the azygous vein.

The azygous vein is a large vessel that enters the proximal superior vena cava and drains blood from the thorax.

Obstruction above the level of the azygous entry point may lead to relatively few symptoms due to the ability of the azygous to decompress the upper extremities, head, and neck.

If a compressive lesion or thrombus obstructs the SVC below the entry point there is no mechanism for upper torso, head, and neck decompression, and patients may present with marked venous collateral formation and facial swelling on examination .

dezsine

Patient’s driver’s license before cancer diagnosis-

Picture 1 year later  

Traditional teaching : most patients present with a sensation of facial fullness, facial swelling, cough, variable arm swelling, and dilated neck and upper chest wall veins, with these it would not be a difficult diagnosis to make.

However, this oncologic entity may present with few if any clinical findings.

Further frequent symptom:

sensation of fullness when bending forward

or a vague, chronic cough.

However, if venous decompression is able to occur, there will be no prominent veins or facial swelling the diagnosis may not even be considered.

Superior vena cava syndrome

Depiction of the azygous vein (denoted by asterisk).  Diagram on the left indicates point at which the azygous enters the SVC and its relationship to intercostal vessels. 

Treatment aim:

alleviating congestive symptoms while simultaneously attempting to make a definitive diagnosis.

In cases where suspected or confirmed lung cancer or lymphoma is the cause, institution of radiation therapy may help lessen venous congestion and reduce upper torso, head, and neck venous pressure.

Previously, superior vena cava syndrome was considered an emergency. Today, emergent radiation therapy should be reserved for patients with life-threatening laryngeal or cerebral edema.

Patients with a confirmed or suspected diagnosis of SVC syndrome

based on clinical grounds should undergo CT scanning

to define the degree of SVC obstruction and

to evaluate for the possibility of thrombotic SVC occlusion (10).

If no known tissue diagnosis of cancer has been done,

a biopsy is typically performed as an outpatient or inpatient.

Adjunctive treatment modalities such as steroids and diuretic therapy

may be used, particularly if head and neck edema is a prominent feature.

Superior vena cava syndrome caused by lung carcinoma.  Notice the ruddy appearance of the patient's face caused by elevation of the arm - Pemberton's sign. 

1. A complaint of facial swelling should be enough to make the emergency physician consider the diagnosis of SVC syndrome. Partial SVC occlusion or compression above the azygous vein may not lead to any physical exam findings.

2. Hoarseness may be a subtle clue when laryngeal edema has developed.

3. Stoke’s sign - Face and neck swelling seen in SVC syndrome

4. Relatively rare but pathognomonic of SVC syndrome is supine facial cyanosis: development of facial cyanosis when the patient is placed in the supine position.

5. Subtle presentations are common and include fatigue (due to poor venous return), dyspnea, chest pain, headache, face and neck swelling, and facial flushing.

6. Incidence of thrombotic SVC syndrome is on the rise.

7. Symptoms tend to be worse upon awakening secondary to venous pooling.

Superior vena cava syndrome

-Clinical presentation of a patient with superior vena cava syndrome.

Injury/Microorganisms

Systemic activation of coagulation

fibrin formationToxins

Activation of-PMN -Macrophage -Endothelium

Cytokines

Microcirculatory disturbances

Organfailure

Microclot formation

Bleeding

Consumption of coagulation factors and inhibitors

Secondary fibrinolysis

DIC

Thrombotic microangiopathies Thrombotic microangiopathies

A THROMBOTIC THROMBOCYTOPENIc PURPURA (TTP) ÉS A THROMBOTIC THROMBOCYTOPENIc PURPURA (TTP) ÉS A HAEMOLYTIC URAEMIC SYNDROM (HUS)A HAEMOLYTIC URAEMIC SYNDROM (HUS)

Have microvascular platelet aggregation in common Have microvascular platelet aggregation in common

But.:But.: TTP can be regarded as a systemic dsorder, TTP can be regarded as a systemic dsorder,

HUS:HUS: is localized to the kidneys.is localized to the kidneys.

TTP és HUS have very many similarities . TTP és HUS have very many similarities .

Similar starting events :….. TTP/HUS complex Similar starting events :….. TTP/HUS complex

TTP and HUS

consumptive thrombocytopenia

microangiopathic haemolytic anaemia

ischaemic symptoms

TTP HUSTTP HUS

Diagnostics, morphology

• Megakaryocytic thrombocytopenia

• Fragmentocytes

Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura ( Moschcowitz syndrome, 1924)( Moschcowitz syndrome, 1924)

Incidence:Incidence: 30 patients have to be treated in Hungary yearly 30 patients have to be treated in Hungary yearly

Mortality of untreated cases : 90-100 %.Mortality of untreated cases : 90-100 %.

A diagnostic criteris: (first 2 criteria are sufficient)A diagnostic criteris: (first 2 criteria are sufficient)

Severe consumptive thrombocytopenia, - plenty of Severe consumptive thrombocytopenia, - plenty of megakaryocytesmegakaryocytes

Fragmentocytic haemolytic anaemia, direct Coombs negFragmentocytic haemolytic anaemia, direct Coombs neg

Fluctuating neurologic symptomsFluctuating neurologic symptoms

Kidney involvement – renal failureKidney involvement – renal failure

FeverFever

TTP – clinical pentade

Moschcowitz: 1924

• consumptiive thrombocytopenia

• microangiopathic hemolytic anaemia

• fluctuating neurológical symptoms

• Kidney involvement – renal failure

• fever

triad: 70-80 %, pentade: 40 %

TTP -frequency

• incidence: 1-7 / 1 million inhabitants / year

• Typical age: 4. decade

• female : male ratio: 3 : 2

• Mortality before1960: > 90 %

• Mortality after 1960 : 5-20 %

TTP – clinical forms

• Acute (single episode) TTP: no relapse

• Intermittent TTP: relapse occurring irregularly

• Chronic cyclic TTP: relapse at regular intervals

Differentialdiagnosis:Differentialdiagnosis:

DICDIC

HELLP sy HELLP sy

ITPITP

Evans syEvans sy

Antiphospholipid syAntiphospholipid sy

Liver diseases Liver diseases

Paroxysmal nocturnal haemoglobinuria (PNH)Paroxysmal nocturnal haemoglobinuria (PNH)

Other causes of mechanical hemolysis (arteficial valve, Other causes of mechanical hemolysis (arteficial valve, etc.)etc.)

Haemolytic uremic syndromeHaemolytic uremic syndrome

A diagnostic criteria:A diagnostic criteria: all the three have to be present) all the three have to be present)

Thrombocytopenia, number megakaryocytes in the BM normal or Thrombocytopenia, number megakaryocytes in the BM normal or increased.increased.

Fragmentocytic haemolytic anaemia, a direkt Coombs test negatíve Fragmentocytic haemolytic anaemia, a direkt Coombs test negatíve (kivéve: neuraminidase infekciókhoz társuló secunder formák).(kivéve: neuraminidase infekciókhoz társuló secunder formák).

Variable degree of kidney involvement, kidney failure Variable degree of kidney involvement, kidney failure

Clinical forms:Clinical forms:

Diarrhoea-asszociated or típical HUSDiarrhoea-asszociated or típical HUS: benign form,: benign form,mortality less than 10 % . mortality less than 10 % .

Sporadic or atypical HUSSporadic or atypical HUS, high mortality, (ca..70 %.), high mortality, (ca..70 %.)no accurate data on incidence. no accurate data on incidence.

Treatment of Treatment of TTP TTP and and HUS HUS • aim:aim: curative. curative.

• Only in hospitals with intensive care units Only in hospitals with intensive care units

• Treatment:Treatment: Plasmaexchange, daily,, substitution with fresh Plasmaexchange, daily,, substitution with fresh frozen plazma or cryo-supernatant frozen plazma or cryo-supernatant : : thus thus 80-90 % 80-90 % of patients might be cured. of patients might be cured.

Alternativ therapy:Alternativ therapy: Fresh frozen plasma or infusion of fresh frozen Fresh frozen plasma or infusion of fresh frozen plasma: plasma: signifivcatnlyx less effective than plasma exchange, signifivcatnlyx less effective than plasma exchange,

Futher drug therapies Futher drug therapies - - CorticosteroidsCorticosteroids- Thrombocyta aggregácion inhibitors?- Thrombocyta aggregácion inhibitors?- Vincristine- Vincristine- Immunosuppressive drugs- Immunosuppressive drugs- potentially high dose iv. Ig - potentially high dose iv. Ig

Supportív therapy:Supportív therapy:

• RBC transfusion, RBC transfusion,

• Platelet transfusion is usually cPlatelet transfusion is usually contraindicatedontraindicated!!

• Treatment of infectionsTreatment of infections

• DialysisDialysis

• Intensive care unit (ritkán gépi lélegeztetés, parenterális Intensive care unit (ritkán gépi lélegeztetés, parenterális táplálás)táplálás)

• Treatment of precipitating cause in the case of secondary Treatment of precipitating cause in the case of secondary formsforms

Hematological indications of apheresis I.Hematological indications of apheresis I.HyperleukocytosisHyperleukocytosis 1.1. LeukostasisLeukostasis

2.2. High peripheral cell counts + chemotherapy causing High peripheral cell counts + chemotherapy causing acute cytolysis acute cytolysis

3.3. High peripheral cell counts + organomegaly causing High peripheral cell counts + organomegaly causing severe compression symptoms severe compression symptoms

4.4. Extremely hig cell numbersExtremely hig cell numbersa. myeloproliferatív sy:a. myeloproliferatív sy: WBC > 300 G/lWBC > 300 G/lb. lymphoproliferatív sy:b. lymphoproliferatív sy: WBC > 500 G/lWBC > 500 G/l

ThrombocytosisThrombocytosis 1.1. With complications (threatening ot manifestWith complications (threatening ot manifestthrombosis and/or bleedingthrombosis and/or bleeding

2.2. plt > 1000 G/l + pregnancyplt > 1000 G/l + pregnancy3.3. plt > 1000 G/l + before a planned operation or plt > 1000 G/l + before a planned operation or

coronarography ( maximally 2 aphereses végezhető)coronarography ( maximally 2 aphereses végezhető)4.4. thr > 1000 G/l + thrombophilia proven by a thr > 1000 G/l + thrombophilia proven by a

laboratory testlaboratory test

TTPTTP Apheresis shlould be stopped in the case of Apheresis shlould be stopped in the case of hematological remission or (brain)deathhematological remission or (brain)death

HUS

Gasser: 1955

• consumptive thrombocytopenia

• microangiopathic haemolytic anaemia

• Acute renal failure

Typical HUS(diarrhoea associated)

• verotoxin / shigatoxin

• Characteristic prodromal phase

• endemic

• Young age (< 5 years)

• low mortality

• rare relapse following kideny transplantation

Sporadic (atypical) HUS(not diarrhoea associated)

• not verotoxin / shigatoxin associated

• No characteristic prodromal phase

• not endemic

• elder age (> 5 years)

• high mortality

• frequent relapse following kidney transplantation

Etiology• idiopathic• familiar• secundary

– infections: verotoxin / shigatoxinneuraminidaseHIVother

– Pregnancy and postpartum period

– Autoimmune disorders

– tumors, chemoterápy– drug: kinin, ticlopidin, (clopidogrel), cyclosporin,

tacrolimus, mitomycin, contraceptives, stb

– Allogeneic stem cell transplantation

Feltételezett pathomechanizmus • prostacyclin termelés zavarai• csökkent fibrinolysis• exogen toxinok, enzimek• thr aggregáló faktorok

– pap37– calpain

• endothel sejt apoptosis• autoimmun mechanizmus

– autoantitest: endothel, CD36– immunkomplex

• vWF eltérései

Jelenlegi hypothesis• TTP-s microthrombosisok: vWF + thr

• kóros vWF multimer eloszlás (ULvW)

• nyíróerő: vWF - direkt thr aggregáció

• áramlási cytometria: thr-hoz kötött vWF

• FFP vagy cryofelülúszó transzfúziója– klinikai remissio

– vWF multimer eloszlás normalizálódása

• vWF cleaving protease: ADAMTS13

(a distintegrin and metalloprotease with eight

thrombospondin-1-like domains) 9q34 kromoszóma

• ADAMTS13 enzimaktivitás csökkenése/hiánya– autoantitest - ADAMTS13 enzim inhibitor

– congenitális enzimhiány

VWF Cleaving Protease(ADAMTS13)

CUBCUBS MMP CysCysDD SpacerSpacer11 22 33 44 55 66 77 88 CUBCUB

Metalloprotease

Disintegrin

Thrombospondin 1

A Disintegrin-like And Metalloproteasewith ThromboSpondin-1 repeats

Laboratory abnormalities.

• microangiopathic haemolytic anaemia– fragmentocytosis, nucleated RBCs– basophil punctation– reticulocytosis– negatív direct Coombs teszt– Slightly elevated indirekt se-bi– Reduced or non-detectable serum haptoglobin– haemoglobinuria, haemosiderinuria

• thrombocytopenia– thr << 50 G/l (TTP)– thr < 100 G/l (HUS)

Laboratory abnormalities - 2

• Significantly elvated serum-LDH (2-20x)• se-kreatinin

– variable (TTP)– increased (HUS)

• Hemostatic abnormalities– normál prothrombin, PTI, fibrinogén

• Urine– haematuria, proteinuria, cylinders

• CRP: normal or slightly increased• Liver enzymes: normal or slightly increased

Differentialdiagnosis

• TTP or HUS

• DIC

• (pre)eclampsia / HELLP sy

• systemic vasculitides

• thrombocytopenia or haemolysis of other causes

Treatment results – empiric plasma therapy

Idiopathic TTP/HUS

• complete haematological remission: 80-95 %

• Relapse within 10 years: 30-40 %

Secundary TTP/HUS

• Variable, depends on underlying cause

Evidence based plasmaexchange since the early 1990-s

• 1970-1990: plazmaexchange / plasma transfusion• 1990---- : prospektíve randomized controlled study

plasmaexhange or plazma transfusion?

- Rock: N Engl J Med 1991;325:393

- Henon: Transfus Sci 1992; 13:63

PLASMAEXCHANGE!

Hematological indications of aHematological indications of apheresispheresis – II. – II.

HUSHUS 1.1. All adult casesAll adult cases2.2. Childhood atypical HUSChildhood atypical HUS3.3. Childhood therapy resistant HUSChildhood therapy resistant HUS

Apheresis should be stopped at the time of Apheresis should be stopped at the time of haematoligical remission independent of the renal statushaematoligical remission independent of the renal status

HELLP syHELLP sy thrombocytopenia, haemolysis, SGOT >70 U/l,thrombocytopenia, haemolysis, SGOT >70 U/l,LDH>600 U/l, LDH>600 U/l, ifif::

1.1. Symptoms persist 24-72 hours follwing termiantion Symptoms persist 24-72 hours follwing termiantion of pregnancy resistant to conservative treatment of pregnancy resistant to conservative treatment

2.2. With postpartum eclampsiaWith postpartum eclampsia

The usual gynecologic causes of DIC should be excluded The usual gynecologic causes of DIC should be excluded before start of apheresisbefore start of apheresis

Hematologial indication of apheresis – III.Hematologial indication of apheresis – III.

GammopathiesGammopathies 1.1. hyperproteinaemia: total protein > 100 g/hyperproteinaemia: total protein > 100 g/

2.2. hyperviscosity sy: blood viscosity is more than 15 hyperviscosity sy: blood viscosity is more than 15 % above what is normal for the given Ht % above what is normal for the given Ht

3.3. Acute renal failure caused by paraprotein Acute renal failure caused by paraprotein

4.4. polyneuropathy polyneuropathy

CryoglobulinaemiaCryoglobulinaemia kryokrit > 1 %, kryokrit > 1 %, ifif1.1. Raynaud sy and/or necrotising cutan vasculitisRaynaud sy and/or necrotising cutan vasculitis2.2. cryoglobulinaemic vasculitiscryoglobulinaemic vasculitis

Cold type AIHACold type AIHA haemolytic crisishaemolytic crisis

Masszíve intravasalMasszíve intravasalhaemolysishaemolysis

Impending renal failureImpending renal failure

Hypercalcaemia malignus betegségekbenHypercalcaemia malignus betegségekbenÁltalános jellemzőkÁltalános jellemzők

calcitriol-mediált PTH-rp mediált (HHM)

lokális osteolízis

tumor fajta mal. lymphomák(Hodgkin-kór,NHL)

epidermalis tumor vesetumormammacarcinoma, ...

- myeloma csontbetegség-solid tumorok csontmetastasisai (tüdő-, mammatu.)

tumor lokalizációja ált. kiterjedt(előrehaladott klinikai stádium)

lokális, ritkábban metastatizáló

lokális

főbb mediátorok calcitriol(1,25OH2D3 vit.)

PTH-related peptid citokinek (IL-1, TNF, LT- , IL-6, TGF-)

a mediátorok hatásmechanizmusa

szisztémás,humorális

szisztémás, humorális

lokális,parakrin

Hypercalcaemia non-Hodgkin lymphomákbanHypercalcaemia non-Hodgkin lymphomákban

Gyakorisága:Gyakorisága: összes NHL 4%-a (9/219)összes NHL 4%-a (9/219)

(kifejezett mal. NHL: 30%)(kifejezett mal. NHL: 30%)

Mechanizmusa:Mechanizmusa: calcitriol-mediált (19 esetben egyidejűcalcitriol-mediált (19 esetben egyidejű

hypercalcaemia és hypercalcitriolaemia)hypercalcaemia és hypercalcitriolaemia)

a növekedett calcitriol szint valószínűleg a növekedett calcitriol szint valószínűleg

extrarenalis eredetűextrarenalis eredetű

nincs jellemző csontváltozásnincs jellemző csontváltozás

In patients taking salicilates, ticlopidin or clopidogrel, In patients taking salicilates, ticlopidin or clopidogrel,

no operation should be performed ( no stomatological no operation should be performed ( no stomatological

procedure!)procedure!)

A calcitriol-mediált hypercalcaemia kezeléseA calcitriol-mediált hypercalcaemia kezelése

corticosteroid önmagában is hatásos corticosteroid önmagában is hatásos

további kezelési lehetőségektovábbi kezelési lehetőségek

- CsontokbólCsontokból calciummobilizáció gátlásacalciummobilizáció gátlása

(osteoclastok gátlása:(osteoclastok gátlása: calcitonin, biszfoszfonátok)calcitonin, biszfoszfonátok)

- bélből calciumfelszívódás csökkentése:bélből calciumfelszívódás csökkentése: Ca szegény étrendCa szegény étrend

- renalis calciumürítés csökkentéserenalis calciumürítés csökkentése hypovolaemia korrekcióhypovolaemia korrekció

FONTOS TOVÁBBÁ:FONTOS TOVÁBBÁ: - UV sugárzás kerülése- UV sugárzás kerülése

- D vitamin bevitel kerülése- D vitamin bevitel kerülése

Ferezissel eltávolított leukémiás massza ( 10 l feletti) CML blasztos fázisban diagnosztizált 34 éves beteg esetében