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Hematologic problems in
psychosomatic medicine
psychiatric clinic of north america
DR. Yasser Alhathial team
Presented by:
Ali bahathig
Introduction:
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The consultation psychiatric is frequently called
assess patients in medical settings
primary or secondary hematologic disorders.
This article adresses psychiatric issues
→ specific to patients who have selected
hematologic disorders, including:
→ B12
→ folate dificency
→ sikle cell disease
→ Hemophilia
Finally, a review of hematologic side effects of
psychotropic medication is also included.
B12 & FOLATE DEFICIENCY:
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B12 & folate deficincy have similar consequences:
→ Nervous system
→ Megaloblastic anemia
Both are cofactors for conversion:
Homocysteine → Methionine
Deficiency of both corrolate with:
↑ Homocysteine level
→ C.V.S, STROKE, DEMENTIA &
ALzheimer’s disease
↑ Homocysteine level & ↓ of B12 & folate:
also associared with depression.
Vitamin B12
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Necessary coenzyme & cofactor in virous reaction:
→ synthesis of DNA + methionine
Epidemiologic studies:
→ prevalence of about 20% in general population
→ number of geriatric individuals → even higher
→ common in psychiatric populations.
Pernicious anemia → B12 deficiency
→ Autoimmune disorder
→ associated with other autoimmune disorder:
→ thyroiditis, DM, grave’s disease…….
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Dietary B12 deficiency is rare
Food or oral-cobalamin malabsorption may caused
by: H. pylori infection
Intestinal overgrowth → antibiotics
chronic use of metformin, antacids, H-2 blocker,
PPI, alcoholism and gastric surgery
Vitamin B12 Malabsorption results from:
→ Gastrectomy
→ Ileal diseases
→ Bowel resection
→ Crohn’s disease
Clinical Manifestation:
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Hematologic manifestation:
megaloblastic anemia
macrocytosis with hypersegmented
polymorphonuclear leuckocytes
thrombocytopenia
leukopenia and pancytopenia
Gastrointestinal manifestation:
intestinal metaplasia
Hunter’s glossitis
Diarrhea and jaundice.
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Neuropschiatric manifestation:
→ common in B12 deficiency → in the elderly
→ may precede hematologic signs
→ symmetrical peripheral neuropathy
→ paresthesias & numbness
→ subacute combined degeneration (SCD)
→ less common
→ posterior & lateral column disruption
→ loss of vibration & position sense
→ ataxia, weaknees & spasticity
rare manifestation: optic neuritis or atrophy
& incontinence
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Psychiatric manifestation:
→ mood changes
→ psychosis
→ cognitive impairment
→ obsessive – compulsive disorder
B12 deficiency is a common cause of
→ potentially reversible dementia &
confusion
Diagnosis and treatment:
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Low normal serum B12 + megaloblastic anemia
or typical neuropsychiatric findings
→ further investigation
Low normal level between 150ng ⁄L to 200ng ⁄ L
Intrinstic factor Ab, serum gastrin:
→ Pernicious anemia
Treatment recommendation:
1000 microgram IM of hydroxycobalamin or
cyanocobalamin daily for 1 ⁄ 52
then maintenence dose 1 ⁄ 12 or Q 3 ⁄ 52
Oral replacement also is effective
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Remission is typically achived in weeks
But, continued maintenance therpy is recommended
→ replete body stores
→ maintain longer period of remmsion
Significant improvement of neuropsychiatric function
has been shown after B12 adminstration.
Degree of recovery → symptom severity
Adminstration of folate only to correct macrocytic
anemia (unrecognized B12 deficiency )
→ will reverse the hematologic abnormalities
→ but neurologic impairment may continue
→ leading to irreversible deficits
Folic acid:
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Folate is important in mood & cognition, brain
growth, differentiation, development & repair.
These mechanisms:
→ nucleotide synthesis
→ DNA transcription & integrity
Folate may protect agnist:
→ certain cancers
→ heart disease
→ birth defects
→ dementia
Presumably via the lowering homocysteine
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Folate deficiency:
→ inadequate diet, alcoholism, chronic illness
→ drugs ( phenytoin, valproic acid, lamotrigine
barbiturates, oral contraceptive )
→ malabsorption
More common in the elderly
More prevalent in psychiatric inpatients compared
with patients without psychiatric illness
(controlling for drug & alcohol abuse)
One third of psychiatric patients, especially with
depression
Clinical manifestations:
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Symptoms of folate deficiency are similar of B12
SCD is specific to B12 deficiency
Depression is more common in folate deficiency
Insufficient folate during conception & eraly
pregnancy results:
neural tube defects (NTD)
Folate deficiency is invariably accompanied by:
↑ Plasma homocysteine level
↑ Risk CVS disease,
Dementia
Depression
Diagnosis & treatment:
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Low RBC folate + ↑ plasma homocysteine
→ is good standard for the diagnosis
more accurate than measuring serum folate alone
No clear guidelines for the dose or duration
→ folate therapy for nervous system disorder
Treatment is recommended for at least 6 months
To ↓ risk of NTDs:
0.4 mg daily is recommended
for woman at high risk:
4-5 mg dialy is recommended
→ one month at least prior to conception
→ through at least first trimester of pregnancy
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In depressed patients:
→ low folate levels → higher levels of depression
→ less likely to respond to antidepressants
Coppen showed that supplementation of:
fluoxetine + folic acid
→ improved antidepressant response
→ concurrent ↓ in plasma homocysteine level
→ not necessarily to ↑ plasma folate level
Sickle cell disease (SCD):
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SCD is the most common hemoglobinopathy
The vaso-occulsive crisis is the hallmark of SCD
→ acute episodes of severe pain
→ extreme of temperature, infectious illness,
→ dehydration and physical exertion may
→ precipitate crises but,
majority of crises → without an identifiable cause
Vaso-occulsive produce:
→ acute pain → in short term
→ end-organ damage → in long term
( bone, kidney, lungs, eyes & brain)
Many patients suffer from chronic pain
as result of avascular necrosis or leg ulcer
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The neuropsychiatric manifestation of SCD
can be grouped in three main categories:
→ 1- depression and anxiety
→ 2- problems with substance abuse
& dependence
→ 3- central nervous system damage
These issues are further complicated by the
poor psychosocial circumstances
Depression and anxiety:
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Prevalence of depression is about 26%
Anxiety disorders have been reported to be 7.1%
Children with SCD have ↑ prevalence:
excessive fatigue, physical complaints & impaired
self-esteem
These feeling arise:
→ frequent hospitalization
→ absences from school
→ inability to experience a normal childhood
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Adults with SCD face:
→ physical deformities + stigma of addiction
→ the consequences of facing these stigma:
self-deprivation, self-hate, suspiciousness,
depression and anxiety
Physical deformities:
→ delayed growth
→ chronic hemolysis & vaso-occlusion
→ problem with self-esteem
→ dissatisfaction with body image
→ social isolation
→ participation in athletic is limited
Chronic & acute pain:
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Patients experiences 0.8% episodes per year.
However, 1% of patient experiences more than 6
episodes per year.
Nature of pain, which has been reported to be as
severe as childbirth
In last 15 years, opioid treatment has been used
widely for SCD pain
→ control pain
→ improve function capacity
→ decrease hospitalization
Substance dependence & addiction behaviors
difficult to define in any chronic pain condition
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Few studies that address addiction in SCD report a
low prevalence
Despite this lack of evidence in medical literature
medical practitioners often overestimate addiction
Studies demonstrate:
→ 63% of nurse believe addiction is prevalent
→ 53% of ER physicians
→ 23% of hematologist though more than 20%
Fear of iatrogenic addiction,
→ physicians may under treat pain
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As a result of under treatment, patient may develop
a pseudo-addcition
(addiction like behavior occur → inadequate pain)
May seek illegal narcotics to manage their pain
→ long-term problems with true addiction
Some patients may inappropriately use opioid in
non pain symptoms:
→ insomnia
→ depression
→ anxiety
In recent studies, 31.4% of adult SCD were found to
abuse alcohol
Central nervous system
damage:
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Brain disease from SCD complication
begins early in life → neurocognitive dysfunction
25-33% of children with SCD have CNS effects
Seizures occur in 12-14% of SCD patients
→ often lead to stroke
CVA occur in 10-15% of SCD children
These demonstrate:
→ intellectual deficits
(ranging from borderline to moderate MR)
→ reduced language function
→ problem with adjustment
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Cognitive deficits in SCD children can lead to:
→ educational problems
→ Intellectual impairment
→ verbal problems
→ problems with attention and concentration
→ dementia later in life
Hemophilia:
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Hemophilia is a bleeding disorder
→ deficiency of the coagulation factors
Hemophilia A (factor VIII)
Hemophilia B (factor IX)
→ well known inherited bleeding disorders
→ clinically, indistinguishable from one another
X-linked & mainly affects males
Classification: severe
moderate
mild
Useful for predicting bleeding tendency and
prognosis
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Severe hemophilia ( < 1% clotting factor)
bleed spontaneously into:
→ joints
→ muscles
→ soft tissues
→ body cavities
Neonatal periods:
→1-4% risk of developing intracranial
hemorrhage
Most children are asymptomatic
→ until they start crawling
→ bruise easily and bleed following minor
injuries
(family of these children → child abuse)
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By age of 4 years most children experience
→ bleed into a joint
Adult experience recurrent bleed into:
→ large joints & muscles
→ joint bleeding →severe acute pain
Repeated bleed lead to destruction:
→ cartilage
→ bone
→ muscle wasting
→ chronic pain
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Moderate hemophilia (1-5% clotting factor):
→ typically diagnosed by the age of 5 years
→ bleeding episodes occur less frequently
Mild hemophilia (> than 5% clotting factor)
→ diagnosed later following trauma, tooth extraction
or surgery
→ spontaneous bleeding is rare
In 1990s, more than 80% of severe hemophilia
patients were infected with viral illnesses
→ HIV, hepatitis B & C
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In children & adolescents higher rate of anxiety
disorder have been reported in hemophilic than
asthmatics
Physician are reluctant to prescribe opiates
→ despite the severe pain
Individual, group and family psychotherapy
→ useful psychotherapeutic
Caution is needed in prescribing psychotropic
→ dose of antidepressant, antipsychotic & opiate
→ reduced to compensate for hepatic impairment
→ may ↑ the risk of bleeding
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Hemophilia & AIDS patients face many stressors:
→ opportunistic infection
→ physical wasting, declining health, chronic pain
→ CNS complications…….
Mother of HIV +ve hemophilic more distressed than
mother of HIV –ve hempphilic
After death from AIDS, bereaved families:
→ extensive psychologic counseling & support
Study in Japan found → 7-9 years after death
bereaved family members → deep sorrow & grief
→ regret, anger, guilt
70% of bereaved family → restricting daily activities
50% of bereaved family → mental heath problems
Hematologic side effects & drug
interaction of psychotropic agents:
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Antipsychotic:
→ aripiprazole & ziprasidone
→ do not have → hematologic side effects
Agranulocytosis is rare → most common & serious
Low potency > high potency
Clozapine causes agrnulocytosis → 0.8 %
→ highest risk in → first 6 months → ↓ significantly
→ case fatality rate → 4.2-16%
(growth stimulating factor GSF)
→ Weekly WBC count is necessary
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If WBC count < 2000/mm
or absolute neutrophil count < 1000/mm
→ immediate cessation of clozapine
Stopping clozapine → recovery in WBC in 3 weeks
Mortality risk associated with agranulocytosis
→ ↑ if infection occur while still on the drug
As Clozapine cause bone marrow suppression:
→ GSFs → normal bone marrow production
Potential hematologic side effects:
→ aplastic anemia, neutropenia, eosinophilia
→ thrombocytopenia
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Antidepressants:
SSRIs inhibit platelet function → bruising & bleeding
→ especially → with aspirin or NSAIDs
SSRIs:
↑ CNS serotonin
↓ platelets serotonin → ↓ platelets aggregation
Upper GIT bleeding may occur at a frequency from
1 in100 to 1 in 1000 patient-year exposure to highaffinity drugs with SSRIs → elderly
Caution is advised in patient at high risk of GI
bleeding
→ consider prescribing a antidepressant
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Patients taking SSRIs should generally use
→ smaller doses or avoid aspirin or NSAIDs
Risk of GI bleeding
→ highest among patients on both SSRIs & NSAIDs
While the evidence to date
→ SSRIs do not cause intracranial bleeding
→ there is a report that patients taking
→ SSRIs along with statins
→ higher risk for subarachnoid hemorrhage
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While some reviews have concluded there is
→ no ↑ risk of combining SSRIs with warfarin
→ case reports of bleeding with concomitant use
of SSRIs & warfarin
Fluoxetine is the most commonly offending agents.
Interactions between warfarin & SSRIs
→ potentially serious consequences
→ enhanced or reduced anticoagulant activity
The possible mechanisms → cytochrome p450
Fluoxetine, fluvoxamine, paroxetine
→ highest potential → interaction
Citalopram, nefazodone, sertraline
→ relatively less likely to interact with warfarin
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Agrnulocytosis due to TCAs is a rare
Idiosyncratic condition → bone marrow toxicity
Lower frequency than antipsychotic
Agrnulocytosis has been associated:
→ imipramine
→ clomipramine
→ desipramine
Clomipramine-induced agranulocytosis
→ recombinant granulocyte colony-stimulating factor
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Benzodiazepines:
Agrnulocytosis has rarely been reported
No causal relationship has been established
No relationship between daily dose or total
cumulative dose & occurrence of hematologic side
effects
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Lithium:
Lithium stimulate leukocytosis with true proliferative
response
In patients on lithium therapy:
documented increases in the:
→ number of platelet
→ platelet serotonin & histamine levels
Lithium-induced hematologic side effects
→ manage hematologic toxicities associated with
other agent & disorder
Patients with persistent leucopenia &thrombocytopenia
following chemotherapy or radiotherapy
→ can be treated with lithium
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Anticonvulsants & mood stabilizers:
Carbamazepine should be avoided
→ history of bone marrow depression
→ Produce a transient reduction in WBCs
→10% of patients during first 4 months
Very rarely it causes potentially:
→ fatal agranulocytosis
→ aplastic anemia
Baseline CBC count → advised before starting
If the WBCs count drop below 3500/mm
→ carbamazepine should be stopped
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Carbamazepine stimulate it’s own metabolism
→ after being taken for a period of time
→ suddenly decrease
Induce hepatic metabolism
→ reduces the anticoagulant effect of warfarin
→ Carbamazepine level & INR will need to be
monitored frequently
Neutropenia, thrombocytopenia & macrocytic
anemia
→ have been associated with valproate
Lamotrigine may also cause agrnulocytosis
All anticonvulsants should be discontinued when
the WBCs count drop below 3000/mm
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