Bad Blood

Abstract

A 48-year-old man with a history of pancreatic cancer who underwent distal pancreatectomy and splenectomy 4 months ago presents with fatigue, weakness, pallor, and dyspnea on exertion. On hospital admission, the patient is found to be severely anemic with a hemoglobin (Hgb) of 5.6 g/dL and a lactate dehydrogenase (LDH) level of 1180 U/L, total bilirubin level of 6.4 mg/dL, haptoglobin level less than 7 mg/dL, and a reticulocyte count of 16.2%. The blood bank history shows that the patient had received two units of red blood cells (RBCs) post pancreatectomy (one on postoperative day #1 and the second on postoperative day #2); the preoperative antibody screen was negative. A type and screen (ethylenediaminetetraacetic acid [EDTA] anticoagulant) sample is submitted to the blood bank along with a request for crossmatch of two units of RBCs for transfusion.

Clinical History

A 48-year-old man with a history of pancreatic cancer who underwent distal pancreatectomy and splenectomy 4 months ago presents with fatigue, weakness, pallor, and dyspnea on exertion. On hospital admission, the patient is found to be severely anemic with a hemoglobin (Hgb) of 5.6 g/dL and a lactate dehydrogenase (LDH) level of 1180 U/L, total bilirubin level of 6.4 mg/dL, haptoglobin level less than 7 mg/dL, and a reticulocyte count of 16.2%. The blood bank history shows that the patient had received two units of red blood cells (RBCs) post pancreatectomy (one on postoperative day #1 and the second on postoperative day #2); the preoperative antibody screen was negative. A type and screen (ethylenediaminetetraacetic acid [EDTA] anticoagulant) sample is submitted to the blood bank along with a request for crossmatch of two units of RBCs for transfusion.

ABO/Rh/Antibody Screen

ABO/Rh (gel method)
Patient RBCs (forward typing)			Patient plasma (reverse typing)
Anti-A	Anti-B	Anti-D	A1 cells	B cells
0	4+	0	4+	0
Antibody screen (AHG/Gel method)
SC1	3+
SC2	3+

1. Reaction scale = 0 (no reaction) to 4+ (strong reaction)

Gel Panel

		Rh-hr								Kell						Duffy		Kidd		Lewis		MNS				P	Lutheran		Test results
Cell #	Rh-hr	D	C	E	c	e	f	C w	V	K	k	Kp a	Kp b	Js a	Js b	Fy a	Fy b	Jk a	Jk b	Le a	Le b	M	N	S	s	P l	Lu a	Lu b	AHG Gel
1	R 1W R 1	+	+	0	0	+	0	+	0	0	+	0	+	0	+	0	+	+	+	0	+	0	+	+	+	+	0	+	3+
2	R 1 R 1	+	+	0	0	+	0	0	0	+	+	0	+	0	+	+	+	+	0	0	+	+	+	+	+	0	0	+	3+
3	R 2 R 2	+	0	+	+	0	0	0	0	0	+	0	+	0	+	0	+	+	0	0	0	+	0	+	+	+ S	0	+	3+
4	R 0 r	+	0	0	+	+	+	0	+	0	+	0	+	0	+	0	0	0	+	0	0	+	+	+	+	+	0	+	3+
5	r′r	0	+	0	+	+	+	0	0	0	+	0	+	0	+	0	+	0	+	+	0	0	+	0	+	+	0	+	3+
6	r″r	0	0	+	+	+	+	0	0	0	+	0	+	0	+	+	0	0	+	0	+	+	+	+	+	+ W	0	+	3+
7	rr	0	0	0	+	+	+	0	0	+	+	0	+	0	+	0	+	+	+	0	0	+	0	+	+	+ S	0	+	3+
8	rr	0	0	0	+	+	+	0	0	0	+	0	+	0	+	+	+	0	+	+	0	+	+	+	0	+ S	0	+	3+
9	rr	0	0	0	+	+	+	0	0	0	+	+	+	0	+	0	+	+	0	0	+	0	+	0	+	0	0	+	3+
10	rr	0	0	0	+	+	+	0	0	0	+	0	+	0	+	+	0	+	+	0	+	+	+	+	+	+ W	0	+	3+
11	R 1 R 1	+	+	0	0	+	0	0	0	0	+	0	+	0	+	0	+	+	0	0	+	+	0	+	0	+	0	+	3+
Patient cell																													3+

1. Reaction scale = 0 (no reaction) to 4+ (strong reaction); S strong, W weak

DAT profile
Polyspecific	3+	Anti-IgG	3+	Anti-C3d	0

1. Reaction scale = 0 (no reaction) to 4+ (strong reaction)

Acid Eluate Panel

		Rh-hr								Kell						Duffy		Kidd		Lewis		MNS				P	Lutheran		Test results IAT/tube
Cell #	Rh-hr	D	C	E	c	e	f	C w	V	K	k	Kp a	Kp b	Js a	Js b	Fy a	Fy b	Jk a	Jk b	Le a	Le b	M	N	S	s	P l	Lu a	Lu b	AHG	CC
1	R 1W R 1	+	+	0	0	+	0	+	0	0	+	0	+	0	+	0	+	+	+	0	+	0	+	+	+	+	0	+	3+	NT
2	R 1 R 1	+	+	0	0	+	0	0	0	+	+	0	+	0	+	+	+	+	0	0	+	+	+	+	+	0	0	+	3+	NT
3	R 2 R 2	+	0	+	+	0	0	0	0	0	+	0	+	0	+	0	+	+	0	0	0	+	0	+	+	+ S	0	+	3+	NT
4	R 0 r	+	0	0	+	+	+	0	+	0	+	0	+	0	+	0	0	+	0	0	0	+	+	+	+	+	0	+	3+	NT
5	r′r	0	+	0	+	+	+	0	0	0	+	0	+	0	+	0	+	0	+	+	0	0	+	0	+	+	0	+	3+	NT
6	r″r	0	0	+	+	+	+	0	0	0	+	0	+	0	+	+	0	0	+	0	+	+	+	+	+	+ W	0	+	3+	NT
7	rr	0	0	0	+	+	+	0	0	+	+	0	+	0	+	0	+	+	+	0	0	+	0	+	+	+ S	0	+	3+	NT
8	rr	0	0	0	+	+	+	0	0	0	+	0	+	0	+	+	+	0	+	+	0	+	+	+	0	+ S	0	+	3+	NT
9	rr	0	0	0	+	+	+	0	0	0	+	+	+	0	+	0	+	+	0	0	+	0	+	0	+	0	0	+	3+	NT
10	rr	0	0	0	+	+	+	0	0	0	+	0	+	0	+	+	0	+	0	0	+	+	+	+	+	+ W	0	+	3+	NT
11	R 1 R 1	+	+	0	0	+	0	0	0	0	+	0	+	0	+	0	+	+	0	0	+	+	0	+	0	+	0	+	3+	NT
Last wash SC1																													0	2+
Last wash SC2																													0	2+

1. Reaction scale = 0 (no reaction) to 4+ (strong reaction); S strong, W weak

Autoadsorption Panel

		Rh-hr								Kell						Duffy		Kidd		Lewis		MNS				P	Lutheran		Test results IAT/tube
Cell #	Rh-hr	D	C	E	c	e	f	C w	V	K	k	Kp a	Kp b	Js a	Js b	Fy a	Fy b	Jk a	Jk b	Le a	Le b	M	N	S	s	P l	Lu a	Lu b	AHG	CC
1	R 1W R 1	+	+	0	0	+	0	+	0	0	+	0	+	0	+	0	+	+	+	0	+	0	+	+	+	+	0	+	0	2+
2	R 1 R 1	+	+	0	0	+	0	0	0	+	+	0	+	0	+	+	+	+	0	0	+	+	+	+	+	0	0	+	0	2+
3	R 2 R 2	+	0	+	+	0	0	0	0	0	+	0	+	0	+	0	+	+	0	0	0	+	0	+	+	+ S	0	+	0	2+
4	R 0 r	+	0	0	+	+	+	0	+	0	+	0	+	0	+	0	0	+	0	0	0	+	+	+	+	+	0	+	0	2+
5	r′r	0	+	0	+	+	+	0	0	0	+	0	+	0	+	0	+	0	+	+	0	0	+	0	+	+	0	+	0	2+
6	r″r	0	0	+	+	+	+	0	0	0	+	0	+	0	+	+	0	0	+	0	+	+	+	+	+	+ W	0	+	0	2+
7	rr	0	0	0	+	+	+	0	0	+	+	0	+	0	+	0	+	+	+	0	0	+	0	+	+	+ S	0	+	0	2+
8	rr	0	0	0	+	+	+	0	0	0	+	0	+	0	+	+	+	0	+	+	0	+	+	+	0	+ S	0	+	0	2+
9	rr	0	0	0	+	+	+	0	0	0	+	+	+	0	+	0	+	+	0	0	+	0	+	0	+	0	0	+	0	2+
10	rr	0	0	0	+	+	+	0	0	0	+	0	+	0	+	+	0	+	0	0	+	+	+	+	+	+ W	0	+	0	2+
11	R 1 R 1	+	+	0	0	+	0	0	0	0	+	0	+	0	+	0	+	+	0	0	+	+	0	+	0	+	0	+	0	2+
Patient cell																													0	2+

1. Reaction scale = 0 (no reaction) to 4+ (strong reaction); S strong, W weak

Additional History

The patient is transfused one “least incompatible” RBC unit with a subsequent rise in the Hgb to 6.2 g/dL. Treatment with prednisone 1 mg/kg/day is started for “Coombs-positive” hemolytic anemia. The following day, a peripheral blood smear is reviewed as below:

Peripheral blood thin smear: 100× Oil, Wright-Giemsa stain. Photomicrograph credit: Malary Mani, MD, Department of Pathology, Mount Sinai St. Luke’s-West, New York, NY

Further History

Based on the peripheral blood smear findings, further history is obtained. On detailed questioning of the patient, he is noted to be a city dweller who has not traveled to any suburban or rural area within the prior 8 months, and he denies any insect (i.e., tick or mosquito) bites or unusual rashes. The patient denies ever receiving a transfusion of blood or blood products prior to the pancreatic surgery.

Questions

• 1. What is the significant finding on the peripheral blood smear? In consideration of this finding and in light of the patient’s clinical history, what is the most probable source of transmission to the patient? What reporting responsibility does the medical director of the transfusion service have in this case?

• 2. What is the relation of the patient’s immunohematology results to the peripheral blood smear finding?

• 3. How does the patient’s history of receiving a splenectomy as part of his pancreatic cancer surgery affect his current condition?

• 4. Should treatment with therapeutic apheresis be considered for this patient? If so, what type of therapeutic apheresis procedure should be performed?

• 5. What measures have been taken by blood donor centers to prevent what occurred in this case?

Answers

• 1. What is the significant finding on the peripheral blood smear? In consideration of this finding and in light of the patient’s clinical history, what is the most probable source of transmission to the patient? What reporting responsibility does the medical director of the transfusion service have in this case? The peripheral blood smear shows intraerythrocytic, ring-form, protozoan parasites consistent with babesiosis ( Babesia microti ). Given that the patient does not have a significant travel risk or known tick bite, the most probable source of the parasitic infection is one of the postoperative blood transfusions that the patient received (babesiosis is typically transmitted through the bite of the deer tick, Ixodes scapularis, but can be transmitted via blood transfusion or by vertical transmission as well; babesiosis is endemic in parts of the United States [of which B. microti ). species is most common], particularly in the northeast and upper Midwest regions [1]. Based on this, the medical director of the transfusion service must report such transmission to the blood collection facility for further investigation of the involved blood donors. In addition, there may be reporting requirements to the regional and/or local (i.e., state and/or city) departments of health; babesiosis has been classified by the Centers for Disease Control and Prevention (CDC) as a nationally notifiable disease since 2011 [2]. On a technical note, it may be quite difficult to differentiate babesiosis from malaria (in particular, Plasmodium falciparum ) on peripheral blood smear alone, though some features that favor the former are greater variation in ring forms (note the variation in the smear above), lack of hemozoin pigment, absence of schizonts and gametocytes, presence of extraerythrocytic parasites, and the finding of the classic Maltese cross form (which is not often found) [3]. In addition, in the United States, where this case occurred, babesiosis is much more common than malaria. It should also be noted that both thick and thin smears should be examined in actual practice [3].

• 2. What is the relation of the patient’s immunohematology results to the peripheral blood smear finding ? The patient in this case presents with warm autoimmune hemolytic anemia (WAIHA) as evidenced by the clinical, laboratory, and immunohematology findings, including the positive anti-IgG direct antiglobulin test (DAT) result. WAIHA has been described in association with cases of babesiosis [4, 5].

• 3. How does the patient’s history of receiving a splenectomy as part of his pancreatic cancer surgery affect his current condition? Asplenic patients are at increased risk of having more severe infection with babesiosis, as are older and immunocompromised patients (e.g. human immunodeficiency virus [HIV] infection) [5].

• 4. Should treatment with therapeutic apheresis be considered for this patient? If so, what type of therapeutic apheresis ? Yes, RBC exchange transfusion may be considered for a patient with babesiosis infection in conjunction with antimicrobial therapy, particularly when the patient has very high parasitemia (greater than 10%) or when the patient manifests other comorbidities of infection such as hemolysis, disseminated intravascular coagulation (DIC), or pulmonary or renal or hepatic compromise [6]. RBC exchange transfusion is currently classified as a category II level indication (disorders for which apheresis is accepted as second-line therapy, either as a standalone treatment or in conjunction with other modes of treatment) for babesiosis by the American Society for Apheresis (ASFA) [6]. Since this particular patient is at higher risk of more severe infection, as a result of the splenectomy, and depending on the parasite load (which appears to be quite high on the peripheral blood smear), RBC exchange transfusion might be a consideration for the patient in this case.

• 5. What measures have been taken by blood donor centers to prevent what occurred in this case? Although traditionally prospective blood donors have been screened for babesiosis only via the donor health questionnaire, some blood donor centers, particularly those in endemic regions of the United States, more recently have initiated donor testing under investigational protocol; note that the United States Food and Drug Administration [FDA] has approved tests to screen for B. microti ) in human plasma and whole blood samples in March 2018 [2, 7]. These tests include both antibody (IgG arrayed fluorescence immunoassay [AFIA] ) and polymerase chain reaction (PCR) nucleic acid test [NAT]) assay-based testing . Donors who test positive for babesiosis or have a history of babesiosis (even if treated) are permanently deferred from donating blood for another person.